Changes in CSF neurotransmitters in infantile spasms

Cerebrospinal fluid (CSF) from 7 patients with infantile spasms (mean age: 6.7 months) was collected before and after treatment with adrenocorticotropic hormone (ACTH). The concentration of neurotransmitter metabolites was analyzed using high-performance liquid chromatography and compared to the metabolite concentration in the CSF from 7 age-matched controls (mean age: 6.1 months). Pretreatment levels of CSF 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid, 3-methoxy-4-hydroxyphenyl glycol (MHPG), and kynurenine were significantly lower in infantile spasm patients compared to controls. Following treatment, marked increases in 5-HIAA and decreases in kynurenine levels were observed in the CSF of the 5 infants whose seizures were eliminated or reduced by ACTH. In the 2 nonresponders 5-HIAA levels decreased. The level of MHPG was reduced slightly in 5 infants, including the 2 nonresponders, and was increased in 2 responders. CSF homovanillic acid levels increased in 4 infantile spasm infants and decreased in 3 following ACTH. These data demonstrate that the presence of seizures in infantile spasms is associated with a significant decrease in serotonergic activity and that elimination of seizures by ACTH is accompanied by increased serotonin turnover. The simultaneous increase of 5-HIAA and decrease of kynurenine, an alternate metabolite of tryptophan, suggests an underlying disturbance of tryptophan metabolism in infantile spasms. The possibility that elimination of seizures by ACTH may be related to decreased production of certain kynurenine metabolites, particularly quinolinic acid, is discussed.     

Multiphase radon generation and transport in porous materials

Radon generation and transport in porous materials involve solid, liquid, and gas phases in the processes of emanation, diffusion, advection, absorption, and adsorption. Oversimplifications, such as representing moist soil systems by air-phase emanation and transport models, cause theoretical inconsistencies and biases in resulting calculations. Detailed Rn rate balance equations for solid, liquid, and gas phases were analyzed and combined using phase equilibrium constants to derive a single diffusive-advective rate balance equation in the traditional form. The emanation, diffusion, and permeability coefficients in the new equation have expanded definitions and interpretations to include Rn phase transfer. Radon adsorption was characterized by an exponential moisture dependence, and diffusion and permeability constants utilized previous moisture relationships. Correct boundary and interface conditions were defined, and the unified theoretical approach was applied to field data from a diffusion-dominated system and to laboratory data from an advection-dominated system. Measured 222Rn fluxes and concentrations validated the modeled values within the measurement variability in both applications.     

Obstetrician-gynecologists as primary care physicians: The Oregon experience—Early perceptions regarding the effects of legislative action

OBJECTIVE: Our purpose was to assess whether legislative action influenced the role of obstetrician-gynecologists as primary care physicians. STUDY DESIGN: An observational study was performed on the basis of a questionnaire sent to 410 obstetrician-gynecologists and 27 medical directors of managed-care organizations. RESULTS: Of 67% of obstetrician-gynecologists and 96% of medical directors who responded, there was agreement as to the content of primary care, but a minority (38%) of obstetrician-gynecologists identified themselves as primary care providers. A minority of medical directors (35%) felt that obstetrician-gynecologists should serve in that role. Both obstetrician-gynecologists and medical directors felt that legislation had little impact. CONCLUSION: The reticence of obstetrician-gynecologists to assume a major role in primary care appears to be the result of an uneasiness with accepting a more comprehensive role in patient management and gatekeeping. They appear comfortable with the more traditional roles but feel that training and experience has not prepared them well for the management of more complex medical problems. (Am J Obstet Gynecol 1998;178:1222-8.)     

Regional activity of galactose-1-phosphate uridyltransferase in rat brain.

The sp act of galactose-1-phosphate uridyltransferase has been measured in individual regions of adult rat brain to see if site-specific differences in enzyme activity can aid in the understanding of brain abnormalities observed in well-treated galactosemic patients. The sp act in the cerebellum, brain stem, and midbrain were higher than in the cortex, hippocampus, and striatum. Activity in the cerebellum was 2-fold greater than that found in the cortex. Steady state levels of mRNA of the enzyme in the cerebellum were twice that of the cortex corresponding to the ratio of enzyme sp act in the two regions. Measurement of the kinetic parameters in tissue from the cerebellum and cortex revealed that the regional specificity in enzyme activity observed in the brain represents differences in the Vmax. Inhibition of the enzyme by uridine and uridine triphosphate was essentially the same for all regions and was not influenced by the 2-fold differences observed in the levels of enzyme. Inhibition by uridine was significantly greater than that for uridine triphosphate.     

The bioavailability and nonlinear pharmacokinetics of MK-679 in humans

MK-679 (R(?)-3-((3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)(3-(dimethylamino)-3-oxopropyl)thio)methyl)thio(propanoic acid) is a potent and specific LTD₄-receptor antagonist. The disposition of MK-679 was investigated in a three-way crossover study in 12 healthy males receiving single intravenous doses of 75, 250, and 500 mg of MK-679. A greater than proportional increase in the area under the plasma concentration—time curve of MK-679 was observed with increase in dose. The plasma concentration data for each subject fitted well to the differential equations for a two-compartment model with linear tissue distribution and Michaelis-Menten elimination from the central compartment, indicating that the elimination of MK-679 in humans is saturable. In a previous study, the disposition of MK-679 in humans was also dose-dependent when given together with its S(+)-isomer, L-668,018. Thus, the disposition of MK-679 in humans is dose-dependent regardless of the presence of its stereoisomer. Also, the bioavailability of MK-679 was determined in six healthy males receiving simultaneously an oral dose of 250 mg of MK-679 and intravenous infusion of 1 mg ¹⁴C-MK-679. Results of this study indicate that the oral bioavailability of MK-679 is nearly quantitative.