A subpopulation of neurons in the rat rostral nucleus of the solitary tract that project to the parabrachial nucleus express glutamate-like immunoreactivity

In rodents, gustatory information is transmitted from second order neurons in the rostral nucleus of the solitary tract (rNST) to the parabrachial nucleus (PBN) in the pons. The chemical nature of this projection is unknown. Therefore, the goal of the current study was to determine if rNST neurons that project to the PBN express glutamate-like immunoreactivity. Projection neurons were retrogradely labeled following stereotaxic injection of rhodamine-filled latex microspheres into the right PBN of seven rats while glutamate-immunoreactive (GLU-IR) structures were visualized in the same tissue using an immunoperoxidase procedure. The number of single- and double-labeled neurons located in the right (ipsilateral) and left rNST, in each of the nuclear subdivisions as well as their position along the rostral-caudal axis of the rNST was determined. GLU-IR cell bodies were located throughout the rNST. Although the rostral central subdivision contained the highest percentage (33.8%) of GLU-IR perikarya, immunolabeled neurons were most concentrated (number/area of subdivision) within the medial subnucleus. The rostral third of the rNST contained the fewest (20. 5%) and lowest density of GLU-IR cell bodies. The highest percentage of rNST neurons retrogradely labeled from the PBN were located ipsilateral (85.4%) to the pontine injection site, in the middle third of the nucleus (44.2%) and within the rostral central subdivision (52.4%). Overall, 18% of the labeled rNST projection neurons were GLU-IR. The distribution of double-labeled neurons mirrored that of the projection neurons with the largest number located in the ipsilateral rNST (84.5%), middle third of the nucleus (40.5%) and rostral central subdivision (64.7%). These results indicate that glutamate may be a main component of the ascending pathway from the rNST to the PBN. In addition, since GLU-IR neurons were located throughout the rNST and most were not retrogradely-labeled, the current results suggest that glutamate may be an important neurotrans-mitter within the medulla.     

Impulsivity and cigarette smoking: delay discounting in current, never, and ex-smokers

Rationale: Impulsivity is implicated in drug dependence. Recent studies show problems with alcohol and opioid dependence are associated with rapid discounting of the value of delayed outcomes. Furthermore, discounting may be particularly steep for the drug of dependence. Objectives: We determined if these findings could be extended to the behavior of cigarette smokers. In particular, we compared the discounting of hypothetical monetary outcomes by current, never, and ex-smokers of cigarettes. We also examined discounting of delayed hypothetical cigarettes by current smokers. Methods: Current cigarette smokers (n=23), never-smokers (n=22) and ex-smokers (n=21) indicated preference for immediate versus delayed money in a titration procedure that determined indifference points at various delays. The titration procedure was repeated with cigarettes for smokers. The degree to which the delayed outcomes were discounted was estimated with two non-linear decay models: an exponential model and a hyperbolic model. Results: Current smokers discounted the value of delayed money more than did the comparison groups. Never- and ex-smokers did not differ in their discounting of money. For current smokers, delayed cigarettes lost subjective value more rapidly than delayed money. The hyperbolic equation provided better fits to the data than did the exponential equation for 74 out of 89 comparisons. Conclusions: Cigarette smoking, like other forms of drug dependence, is characterized by rapid loss of subjective value for delayed outcomes, particularly for the drug of dependence. Never- and ex-smokers could discount similarly because cigarette smoking is associated with a reversible increase in discounting or due to selection bias. Received: 3 March 1999 / Final version: 11 May 1999     

Organ-to-plasma uptake ratio of Tl-201 in rats injected at rest or after strenuous exercise

A comparison is made of relative organ-to-plasma Tl-201 uptake in rats at rest and after exercise (2 h swimming). Organs were obtained 1/2 or 3 h after Tl-201 injection. Under the four experimental conditions, the largest uptake was found in kidneys, heart and adrenal glands. The post-exercise to rest ratio of myocardial uptake is in agreement with clinical data reported in the literature. Two extensive tissues, skeletal muscle and fat, showed a remarkable increase of Tl-201 uptake at 3 h as compared to 1/2 h in both rested and post-exercised animals. During the same time interval there was a temporal washout of Tl-201 from heart (both at rest and after exercise) and kidney (after exercise only). The findings do not support the view of a delayed myocardial uptake phase of Tl-201 during which Tl-201 would be reintroduced into the blood from other body organs.     

Involvement of deprivation and environmental lead in neural tube defects: a matched case-control study

OBJECTIVE: To analyse the prevalence of neural tube defects in small geographical areas and seek to explain any spatial variations with reference to environmental lead and deprivation. SETTING: The Fylde of Lancashire in the north west of England. DESIGN: Cases were ascertained as part of a prospective survey of major congenital malformations in babies born in the Fylde to residents there between 1957 and 1981. A matched case-control analysis used infants with cardiovascular system, alimentary tract, and urinary system malformations as controls. Conditional logistic regression was used to assess the effects of more than 10 micrograms/l lead in drinking water and the Townsend deprivation score. RESULTS: The prevalence of neural tube defects in 1957-73 was higher in Blackpool, Fleetwood, and North Fylde, whereas the three control groups showed no significant spatial variation. In 1957-81 mothers living in electoral wards with either a higher proportion of houses with more than 10 micrograms/l lead in the water or a higher deprivation score had a greater risk of having a baby with a neural tube defect. For spina bifida and cranium bifidum alone, this was also true. For anencephaly, deprivation was less important although the effect of lead was still seen. In some neural tube defects, lead may act independently of other possible factors associated with deprivation. It seemed unlikely that lead levels changed significantly during the survey. The percentage of houses with 10 micrograms/l or more of lead in the water in 1984-5 was similar to that found in Great Britain 10 years previously. CONCLUSION: There is evidence to suggest that lead is one cause of neural tube defects, especially anencephaly. This could link the known preventive actions of hard water and folic acid. Calcium is a toxicological antagonist of lead. One cause of a deficiency of folic acid is impaired absorption secondary to zinc deficiency, which may be produced or exacerbated by lead.     

Tuberous sclerosis complex and Wolff-Parkinson-White syndrome

This report highlights the association between tuberous sclerosis and Wolff-Parkinson-White syndrome. Ten patients with concurrent diagnoses of Wolff-Parkinson-White syndrome and tuberous sclerosis were identified. Wolff-Parkinson-White syndrome presented early in life, nine cases being diagnosed in the first year. Eight of the 10 cases were male. In eight cases, the syndrome was associated with supraventricular tachycardias, and in nine with cardiac rhabdomyomata. One child died from cardiac failure secondary to obstruction of the left ventricular outflow tract by a rhabdomyoma. Five of nine survivors showed resolution of Wolff-Parkinson-White syndrome on follow up. The accessory pathway was localised in nine patients from surface electrocardiograms: six children had left sided pathways and three had right sided pathways.     

Quantitation of dolastatin-10 using HPLC/electrospray ionization mass spectrometry: application in a phase I clinical trial

A highly sensitive and specific assay for the quantitation of the anticancer agent dolastatin-10 (DOL-10) in human plasma is described. The method was based on the use of electrospray ionization-high-performance liquid chromatography/mass spectrometry (ESP-LC/MS). The analytical procedure involved extraction of plasma samples containing DOL-10 and the internal standard (DOL-15) with n-butyl chloride, which was then evaporated under nitrogen. The residue was dissolved in 50 μl mobile phase and 10 μl was subjected to ESP-LC/MS analysis using a C₁₈ microbore column. A linear gradient using water/acetonitrile was used to keep the retention times of the analytes of interest under 5 min. The method exhibited a linear range from 0.005 to 50 ng/ml with a lower limit of quantitation (LLQ) at 0.005 ng/ml. Absolute recoveries of extracted samples in the 85–90% range were obtained. The method's accuracy (≤5% relative error) and precision (≤10% CV) were well within industry standards. The analytical procedure was applied to extract DOL-10 metabolites from samples obtained following incubation of the drug with an activated S9 rat liver preparation. Two metabolic products were detected and were tentatively identified as a N-demethyl-DOL-10 and hydroxy-DOL-10. Structural assignments were made based on the fragmentation patterns obtained using the electrospray source to produce collision-induced dissociation (CID). The method was also applied to the measurement of DOL-10 in the plasma of patients treated with this drug. Preliminary investigation of the pharmacokinetics suggested that drug distribution and elimination may be best described by a three-compartment model with t_1/2α = 0.087 h, t_1/2β = 0.69 h and t_1/2γ = 8.0 h. Plasma clearance was 3.7 l/h per m². Received: 17 March 1997 / Accepted: 13 June 1997     

Blood-brain barrier and blood volume imaging of cerebral glioma using functional CT: A pictorial review

Five cases of cerebral glioma are presented here that illustrate the benefit of functional CT imaging of blood-brain barrier permeability and cerebral blood volume. Functional CT uses Patlak analysis of a single location dynamic sequence to extract physiological information that is useful clinically in the assessment of cerebral gliomas. Functional CT offers distinct advantages over other functional modalities including clearer delineation of tumour, tumour grading, measurement of tumour activity and monitoring response to therapy.     

Determination of glomerular filtration rate using a dual-detector gamma camera and the geometric mean of renal activity: correlation with the Tc-99m DTPA plasma clearance method

PURPOSE: In this study, the authors studied the use of a dual-detector gamma camera to measure the glomerular filtration rate (GFR). METHODS: Thirty-three patients with a wide range of renal function participated in this study. The GFR was measured using a dual-detector gamma camera by calculating the geometric mean of activity from each kidney and using an outline background. These results were compared with the GFR estimates obtained from Tc-99m DTPA plasma clearance using a multiple blood sample method. RESULTS: Correlation was excellent between GFR estimated using the dual-detector gamma camera and GFR measured using the plasma clearance of Tc-99m DTPA with multiple blood samples (r = 0.89). The correlation was especially strong in children younger than 13 years (r = 0.94). CONCLUSION: Measuring the GFR using a dual-detector gamma camera and calculating the geometric mean of renal activity yields relatively accurate results.