Extracellular serotonin levels change with behavioral state but not with pyrogen-induced hyperthermia.

Extracellular 5-HT in the anterior hypothalamus/preoptic area (AH/POA) and caudate nucleus of the freely moving cat was measured using in vivo brain microdialysis. Administration of 8-OH-DPAT, a 5-HT1A receptor agonist that decreases 5-HT neuronal activity, decreased extracellular 5-HT in both brain areas. Extracellular 5-HT levels were also examined in relationship to the sleep-wake cycle, because previous data from our laboratory have indicated that behavioral state is the primary determinant of 5-HT neuronal discharge. As with 5-HT neuronal discharge, extracellular 5-HT was increased during active behavioral states and decreased during somnolent periods. These first two sets of findings confirm the ability of the microdialysis technique to measure physiological fluctuations in extracellular 5-HT levels and support the hypothesis that neuronal discharge is a major determinant of extracellular 5-HT levels. Levels of the 5-HT metabolite 5-hydroxyindole acetic acid (5-HIAA) in the AH/POA were also responsive to changes in behavioral state and administration of 8-OH-DPAT, though fluctuations in extracellular 5-HIAA were less robust and temporally delayed. Finally, extracellular 5-HT and 5-HIAA were examined in the AH/POA during fever induced by systemic injection of the synthetic pyrogen muramyl dipeptide. Previous data from our laboratory have indicated that 5-HT neuronal activity is unaffected by this manipulation, though 5-HT has been implicated specifically in thermoregulation. Pyrogen-induced hypothermia produced no specific change in 5-HT efflux, because any changes noted could be accounted for by behavioral state changes. These data are consistent with the hypothesis that the brain serotonergic system is closely linked to the sleep-wake-arousal cycle. However, extracellular 5-HT may be involved in thermoregulatory processes as part of a global role in modulating neuronal activity in coordination with the behavioral state of the animal.     

Dependence of blood clot lysis on the mode of transport of urokinase into the clot--a magnetic resonance imaging study in vitro

Magnetic resonance imaging was employed to study the dependence of clot lysing patterns on two different modes of transport of urokinase into whole blood clots. In one group of clots (nonperfused clots, n1 = 10), access of urokinase to the fibrin network was possible by diffusion only, whereas in the other group (perfused clots, n2 = 10) bulk flow of plasma containing urokinase was instituted through occlusive clots by a pressure difference of 3.7 kPa (37 cm H2O) across 3 cm long clots with a diameter of 4 mm. It was determined separately that this pressure difference resulted in a volume flow rate of 5.05 +/- 2.4 x 10(-2) ml/min through occlusive clots. Perfused clots diminished in size significantly in comparison to nonperfused ones already after 20 min (p less than 0.005). Linear regression analysis of two-dimensional clot sizes measured by MRI showed that the rate of lysis was more than 50-times faster in the perfused group in comparison to the nonperfused group. It was concluded that penetration of the thrombolytic agent into clots by perfusion is much more effective than by diffusion. Our results might have some implications for understanding the differences in lysis of arterial and venous thrombi.     

Laterality of cross-modal spatial processing

This study examined the laterality of spatial-form perception in normal adults using a cross-modal matching paradigm involving visual and tactile processing. Randomly generated eight-point and 12-point Vanderplas and Garvin (1959) patterns were used as the stimuli. In a visual-to-tactile task, a lateralized visual pattern was followed immediately by a haptic task requiring subjects to discriminate which of two simultaneously felt shapes matched the visual pattern. In a tactile-to-visual task, subjects decided which of two simultaneously felt shapes matched a lateralized visual pattern presented after haptic manipulation. There were no main effects for laterality or for sex differences. Matching accuracy was better in the visual-to-tactile task and for less complex stimuli. A visual field by feeling hand interaction showed best recognition accuracy when visual-feeling hand combinations on the same side of the body were used in the two matching tasks. These data reflect a stimulus-response compatibility explanation of spatial-form perception that is consistent with a behavioral and not a cerebral asymmetry model.     

Growth of children from 0-5 years: with special reference to mother's smoking in pregnancy

A cohort of 1163 pregnant women in two small towns in South Wales, UK, was identified and followed until the children born to them were five years of age. Growth in these children is described and a number of determinants identified. Social-class differences were very small at birth but differences in height became clear by the age of two years and in head circumference before this. In height the differences were largely accounted for by greater growth in social class I, but there was a gradient in head circumference throughout all the social classes. The social class effects gradually increased as the children became older. Parity of the mothers had a small effect on size at birth but age of the mother had no effect once parity was allowed for. Data on illnesses in the children were collected but no effect on growth could be detected. By far the most important determinant of growth which could be controlled is maternal smoking. About 40% of the women smoked, about 17% heavily (15 or more cigarettes per day) and the prevalence of smoking altered little during pregnancy. There was a graded effect of smoking on growth up to a 9% deficit in birth-weight, a 2% deficit in length at birth and a 1.5% deficit in head circumference in the babies born to the mothers who smoked most heavily (25 or more cigarettes per day) compared with non-smokers. There effects decreased with age but there were still residual effects at age five years.     

Prophylactic long-term oral tocolysis of multiple pregnancies

After admission to hospital for bed rest, 200 women with multiple pregnancies were randomly allocated to receive either 4 mg of salbutamol orally five times daily, or to receive no drug. After an average of 6 weeks treatment, no difference between the experimental groups could be detected with respect to duration of gestation, birthweight or any other of the outcomes of pregnancy observed.     

Pituitary abnormalities in eating disorders: further evidence from MRI studies

1. The frequent occurrence of hypothalamo-pituitary dysfunction in patients with eating disorders as well as prior reports that nutritional and endocrine status influence pituitary morphology, led us to hypothesize that pituitary size and shape may be altered in patients with eating disorders. 2. Magnetic resonance imaging (MRI) does not use ionizing radiation and is currently one of the most feasible modalities available to study the pituitary gland in vivo. Using MRI, we have previously reported in a preliminary study that female patients with eating disorders had significantly smaller pituitary glands than controls. In addition MRI excluded any pituitary mass lesions. 3. In this report, we confirm our previous MRI findings and provide further evidence of pituitary abnormalities in an expanded sample of eating disorder patients. Preliminary data on pituitary volume estimates from MRI scans are provided for a subset of patients and controls.     

Alpha 2-antiplasmin, plasminogen activator inhibitor (PAI) and dilute blood clot lysis time in selected disease states.

This paper is an attempt to assess the relevance of the inhibitors of fibrinolysis for clot lysis in selected disease states and to discuss the mechanisms leading to acquired abnormal levels of such inhibitors. When compared to 20 control subjects the 30 hypertriglyceridemic patients (14 with type IIb and 16 with type IV) displayed significantly (p less than 0.001) increased plasma plasminogen activator inhibitor (PAI) activity (221 +/- 88% and 290 +/- 104% respectively; mean +/- SD), moderately (p less than 0.01) increased alpha 2 antiplasmin (alpha 2AP) level (112 +/- 11% and 115 +/- 16%) and accordingly an obviously prolonged dilute blood clot lysis time (DBCLT). Neither PAI activity and alpha 2AP level nor DBCLT were significantly different from controls in the 10 patients with hyperlipoproteinemia type IIa. The 18 patients with severe hepatic cirrhosis had low alpha 2AP level (59 +/- 19.7%) and accelerated clot lysis, while mean PAI activity (160 +/- 87%) was slightly (p less than 0.05) increased. In the 17 nephrotic patients alpha 2AP was increased (115 +/- 12%) while PAI activity was similar to controls and DBCLT rather shorter. Two liver secretion enzymes, namely serum cholinesterase and plasma protein C, were found to be decreased in cirrhotic patients, similar to control values in hyperlipoproteinemia type IIa and obviously increased in nephrotic patients as well as in hypertriglyceridemic subjects. The relevance of PAI and alpha 2AP for clot lysis was considered in relation to data in the literature concerning the behaviour of t-PA and factor XIII.(ABSTRACT TRUNCATED AT 250 WORDS)