Clinical applications of functional MRI in neuropsychiatry

Clinical neuroimaging is due for yet another sea change as functional neuroimaging becomes increasingly powerful and available. Functional magnetic resonance imaging (fMRI) is perhaps the most promising of the emerging techniques. The following review helps us understand the physics, strengths, limitations, and promise of fMRI. The authors are all affiliated with the Brain Imaging Center at McLean Hospital and with the Departments of Neurology (Dr. Levin) and Psychiatry (Dr. Renshaw) at Harvard Medical School.     

Solitary extra-osseous ovarian plasmacytoma. Apropos of an unusual case in a 12 year old child

A rare case of extramedullary or solitary ovarian plasmocytoma in a 12 years old patient is reported. Surgery consisted of left adnexectomy associated with omentectomy. Chemotherapy with abdomino-pelvic iradiation were effectuated afterwards. Review of literature and therapeutic indications are discussed.     

Gender and haplotype effects upon hematological manifestations of adult sickle cell anemia

We evaluated the rates of short-term neonatal complications, neonatal brain damage or mortality in a group of 96 singleton pregnancies complicated by hypertension and electively delivered before 36 weeks gestation. The neonatal outcome of these pregnancies was compared with that of a matched control group of 192 uneventful pregnancies delivered because of spontaneous preterm labor or premature rupture of membranes. Although the rates of acidosis, apneoic crises, bradycardia and ventilatory support were higher among cases than controls, the risk of intraventricular hemorrhage, severe brain damage (grade III-IV intraventricular hemorrhage or periventricular leucomalacia) or neonatal mortality were comparable between the two groups. Neonatal complications were more frequent among infants born to mothers with severe hypertension or severe proteinuria. In conclusion, this study has shown that short term neonatal complications after elective preterm delivery in hypertensive pregnancies are increased in comparison with low risk controls. However, these complications, which were well managed in our intensive care nursery, did not affected neonatal mortality or severe brain damage.     

Effects of Asp-369 and Arg-372 mutations on heme environment and function in human endothelial nitric-oxide synthase

Eight polar amino acid residues in the putative substrate-binding region from Thr-360 to Val-379 in human endothelial nitric-oxide synthase (eNOS) (Thr-360, Arg-365, Cys-368, Asp-369, Arg-372, Tyr-373, Glu-377, and Asp-378) were individually mutated. Only two of these residues, Asp-369 and Arg-372, were found to be essential for enzyme activity. A further series of mutants was generated by replacing these two residues with various amino acids and the mutant proteins were expressed in a baculovirus system. Mutant eNOS had a very low L-citrulline formation activity with the exception of D369E and R372K, which retained 27% and 44% of the wild-type enzyme activity, respectively. Unlike the wild-type enzyme, all mutants except D369E, R372K, and R372M had a low spin heme (Soret peak at 416 nm). All the Asp-369 mutants had higher Kd values for L-arginine (1-10 mM) than wild-type eNOS (0.4 microM) and an unstable heme-CO complex, and except for D369E, had a very low (6R)-5,6,7, 8-tetrahydro-L-biopterin (BH4) content. In contrast, each of Arg-372 mutants retained a considerable amount of BH4, had a moderate reduction in L-arginine affinity, and had a more stable heme-CO complex. 1-Phenylimidazole did not bind to wild-type eNOS heme, but bound to all Asp-369 and Arg-372 mutants (Kd ranged from 10 to 65 microM) except R372K. Heme spin-state changes caused by binding of 3, 5-lutidine appeared to depend on both charge and size of the side chains of residues 369 and 372. Furthermore, all Asp-369 and Arg-372 mutants were defective in dimer formation. These results suggest that residues Asp-369 and Arg-372 in eNOS play a critical role in oxygenase domain active-site structure and activity.     

Prolactin-releasing effect of buspirone in developing and adult male and female rats

The prolactin-releasing effects of buspirone, an azaspirodecanedione anxiolytic drug unrelated to the benzodiazepines in structure and pharmacologic properties, was examined in developing and adult male and female rats. The possibility that effects of this drug on hormone release could be modulated by neonatal brain sexual differentiation was also evaluated. A single injection of buspirone, 2 or 10 mg/kg body wt, increased serum prolactin (PRL) levels in both sexes; the increase was significant from Day 12 onward. The PRL-releasing effect increased with age. No significant sexual differences were observed in younger rats, but in peripubertal and adult animals, the hyperprolactinemic response was higher in the female. Neonatal androgenization of females or orchidectomy of males failed to modify the PRL-releasing action of buspirone. Serum titers of luteinizing hormone and follicle-stimulating hormone were not modified by buspirone at any age. The present results show for the first time the ontogeny of the PRL-releasing effect of buspirone in male and female rats, and provide evidence that the response is higher in the female and that the effect does not depend on brain sexual differentiation.     

Severe algoneurodystrophy of the right foot associated with prostatic cancer

The authors report 1 case of particularly severe reflex neurovascular dystrophy whose clinical course was marked by the discovery of a carcinoma of the prostate. There was improvement in the reflex neurovascular dystrophy despite hormonal therapy of the cancer. Reflex neurovascular dystrophy cannot be considered as a form of a paraneoplastic syndrome.     

Ultrastructural localization of prostaglandin endoperoxide synthase (cyclooxygenase) to isolated, purified fractions of guinea pig peritoneal macrophage and line 10 hepatocarcinoma cell lipid bodies

The majority of equations used to predict values for basal metabolic rates (BMRs) are the result of indirect calorimetry measurements performed in the 1930s and 1950s. To assess the reliability of these equations in predicting the resting energy expenditure (REE) of the children in our community, indirect calorimetry was performed on 92 male and 107 female healthy children 2-3 h postprandial. Each individual was measured for a duration of 15-20 min. The data for analysis were obtained from 5-15 min steady-state periods. Subjects ranged in age from 5 to 16 years. The results were compared with BMRs calculated from the Harris-Benedict equation (Harris J, Benedict F. A biometric study of basal metabolism in man. Washington, DC: Carnegie Institute of Washington, publication no. 279, 1919.), the Food and Agriculture Organization/World Health Organization/United Nations University (FAO/WHO/UNU) equations, and the equations proposed by Schofield for use by the 1985 FAO/WHO/UNU Nutrition Committee. The values predicted by the FAO/WHO/UNU and Schofield equations were consistent with the measured resting values for all the children in the study population. Ninety-two children weighed between 90-110% of their ideal body weight. When the measured REE and estimated BMR were compared by gender and age in these children, the Schofield equations provided the best estimates. Ninety-four of the study subjects weighed > 110% of their ideal body weight. The predicted estimates by all equations were consistent with the measured values in this subgroup of the population. We conclude that the FAO/WHO/UNU and Schofield equations are reliable estimates of metabolic rate in healthy children when measurement of REE is not possible.