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The pituitary gland: changes on MR images during the 1st year after delivery.

PURPOSE: To longitudinally and prospectively investigate changes in the volume and signal intensity on T1-weighted magnetic resonance (MR) images of the pituitary gland up to 1 year after delivery and evaluate whether termination of lactation has an effect on these parameters. MATERIALS AND METHODS: All participants provided informed consent for participation in the study, which was approved by the institutional review board. Thirteen volunteers (mean age, 28 years; age range, 26-32 years) underwent MR imaging 2 and 4 weeks after delivery and then at intervals of 0.5-2.0 months until 1 year after delivery. Eight participants terminated lactation during the study period. Sagittal and coronal T1-weighted images were obtained. Signal intensities of the anterior and posterior lobes of the pituitary were calculated relative to that of the pons. The volume of the pituitary was also calculated. Two-tailed paired Student t tests and separate simple linear regression analyses were used to test for statistically significant differences. RESULTS: The mean pituitary volume was 544 mm3 at 2 weeks, 523 mm3 at 4 months, 512 mm3 at 8 months, and 511 mm3 at 12 months after delivery, with significant differences between 2 weeks and 4 months (P = .002) and between 4 and 8 months (P = .003) after delivery. The mean ratio of the signal intensity of the anterior lobe of the pituitary to the signal intensity of the pons was 1.11 at 2 weeks, 1.07 at 4 months, 1.03 at 8 months, and 1.00 at 12 months after delivery, with significant differences between 2 weeks and 4 months (P = .004) and between 4 and 8 months (P = .0001) after delivery. Termination of lactation had no statistically significant effect on pituitary volume or the ratio of the signal intensity of the anterior or posterior lobe of the pituitary to the signal intensity of the pons. CONCLUSION: The volume of the pituitary gland decreases up to 8 months after delivery, and the T1-weighted signal intensity of the anterior lobe of the pituitary decreases; termination of lactation has no statistically significant effect on these parameters.

Adult↗

Modulation of the migrating myoelectric complex by brain noradrenergic systems in rats.

The respective role of central and peripheral noradrenergic systems in the control of migrating myoelectric complex (MMC) was investigated in rats following lesions with 6-hydroxydopamine (6-OHDA). 6-OHDA was injected via intraperitoneal (ip), intracisternal (icis), and intracerebroventricular (icv) routes in rats. Control animals received the vehicle alone. One month later, MMC was recorded in conscious rats chronically fitted with electrodes. The MMC period was significantly lengthened after 6-OHDA ip or icv injection, and slightly shortened after 6-OHDA icis injection. No disruption of central noradrenergic systems was detected after ip lesions. Norepinephrine content was reduced in the digestive tract after ip lesions, in the spinal cord after icis lesions, and in the cortex, the hypothalamus, pons-medulla, and the spinal cord after icv lesions. After icis lesions, noradrenergic perikarya were spared in pons-medulla, whereas only pons noradrenergic perikarya were lesioned after icv lesions. We conclude that lesions of brain noradrenergic systems modify MMC periodicity in rats. The rostral noradrenergic systems may play the major modulatory role.

Animals↗

Brain responses associated with the Valsalva maneuver revealed by functional magnetic resonance imaging.

The Valsalva maneuver, a test frequently used to evaluate autonomic function, recruits discrete neural sites. The time courses of neural recruitment relative to accompanying cardiovascular and breathing patterns are unknown. We examined functional magnetic resonance imaging signal changes within the brain to repeated Valsalva maneuvers and correlated these changes with physiological trends. In 12 healthy subjects (age, 30-58 yr), a series of 25 volumes (20 gradient echo echo-planar image slices per volume) was collected using a 1.5-Tesla scanner during a 60-s baseline and 90-s challenge period consisting of three Valsalva maneuvers. Regions of interest were examined for signal intensity changes over baseline and challenge conditions in cardiorespiratory-related regions. In addition, whole brain correlations between signal intensity and heart rate and airway load pressure were performed on a voxel-by-voxel basis. Significant signal changes, correlated with the time course of load pressure and heart rate, emerged within multiple areas, including the amygdala and hippocampus, insular and lateral frontal cortices, dorsal pons, dorsal medulla, lentiform nucleus, and fastigial and dentate nuclei of the cerebellum. Signal intensities peaked early in the Valsalva maneuver within the hippocampus and amygdala, later within the dorsal medulla, pons and midbrain, and deep cerebellar nuclei, and last within the lentiform nuclei and the lateral prefrontal cortex. The ventral pontine signals increased during the challenge, but not in a fashion correlated to load pressure or heart rate. Sites showing little or no correlation included the vermis and medial prefrontal cortex. These data suggest an initiating component arising in rostral brain areas, a later contribution from cerebellar nuclei, basal ganglia, and lateral prefrontal cortex, and a role for the ventral pons in mediating longer term processes.

Adult↗

Chronic maternal hypoxia. Effect of mid-gestational maternal hypoxia on methionine-enkephalin concentrations within pre- and postnatal rabbit brainstem regions.

We examined the effect of chronic maternal hypoxia on methionine-enkephalin concentrations in fetal (gestational day E-28) and neonatal (postnatal days 3, 7, 21) brainstem regions. Pregnant rabbits were housed in environmental chambers at gestational day E-10. Between E-14 and E-28 the pregnant rabbits were separated into two groups. Group I were controls (C) and breathed 21% O2/79% N2 and group II, hypoxia (H), breathed 12-14% O2/86-88% N2. Sacrifice occurred at various days depending on the experimental paridigm. On gestational day E-28, the first group of 6 pregnant animals (3 C, 3 H) were delivered by hysterotomy and the pups were immediately sacrificed. On and after gestational day E-28, the remaining 12 pregnant animals breathed room air. These animals delivered spontaneously between 30 and 32 days of gestation. The pups remained with their mothers until sacrifice. On postnatal days 3, 7, or 21, methionine-enkephalin was measured by radioimmunoassay in the colliculi (fetal animals), superior and inferior colliculi (postnatal animals), pons and medulla (both groups). In both normoxia-exposed and hypoxia-exposed animals, methionine-enkephalin was highest in the medulla, intermediate in the pons, and lowest in the colliculi. Chronic maternal hypoxia significantly increased the methionine-enkephalin concentration in the pons of E-28 fetuses (p less than 0.02). Levels were increased in the medulla as well but these did not reach significance (p = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Melatonin receptors in discrete brain areas of the male rat. Impact of aging on density and on circadian rhythmicity.

The distribution of melatonin receptors in six discrete brain areas of mature (3-4 months old) and aged (greater than 24 months old) male rats was recorded every 4 h during a 24-hour light: dark cycle (L:D 14:10h). 125I-melatonin was used as a melatonin receptor probe. In the mature animals, specific binding of 125I-melatonin was found in all brain areas investigated, i.e. hypothalamus, medulla pons, hippocampus, cerebellum, parietal cortex and striatum. The density of 125I-melatonin-binding sites in the hypothalamus, medulla pons and hippocampus exhibited clear diurnal rhythms with different patterns and phases. No such rhythm was evident in the cerebellum, parietal cortex and striatum. The apparent affinity of the binding sites was similar in all the brain regions and did not change at any of the times recorded. In the old male rats, the density of 125I-melatonin binding sites in the hypothalamus was only 10% of that in the mature animals at 13 h after the onset of light and was vanishingly small throughout the 24-hour period. The 24-hour mean of the binding site density in the parietal cortex, hippocampus and medulla pons was significantly lower than in mature rats with no apparent diurnal variations. The age-related decrease in the density of melatonin-binding sites was less pronounced in the cerebellum and striatum. In all brain areas tested, apart from the hypothalamus, the decrease in receptor densities was not accompanied by changes in the apparent affinity towards the ligand.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Circadian rhythm of cyclic nucleotide and GABA levels in the rat brain.

Daily variation in the levels of cyclic nucleotides and GABA was examined in seven brain regions of male Sprague-Dawley rats. Significant daily rhythm of cyclic AMP levels was found in the cerebellum and pons medulla oblongata. Circadian variation of cyclic GMP levels was found in the cerebellum, cerebral cortex, striatum, and hypothalamus. Daily variation of GABA levels was found in the pons medulla oblongata and striatum. Cyclic GMP in the pons medulla oblongata and GABA in the hypothalamus were found to exhibit ultradian variation of levels. These observed daily fluctuations of baseline levels should be considered when examining the duration of action of various drugs upon these substances.

Animals↗

Effect of methimazole-induced hypothyroidism on multiple opioid receptors in rat brain regions.

The effect of chronic administration of methimazole (0.05% w/v) in drinking water for 32 days to male Sprague-Dawley rats on the binding of opioid ligands, 3H-Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGO, mu-receptors), 3H-Tyr-D-Ser-Gly-Phe-Leu-Thr (DSTLE, delta-receptors) and 3H-ethylketocyclazocine (EKC, kappa-receptors) to membranes of brain regions was determined. Chronic administration of methimazole to rats decreased their rate of body weight gain, colonic temperature, systolic blood pressure and heart rate in comparison to vehicle-treated rats. Administration of methimazole also decreased the serum concentration of triiodothyronine (total T3) and T4 when compared to vehicle-treated rats. The binding of 3H-DAGO to membranes of amygdala, pons and medulla, striatum, midbrain and cortex of methimazole-treated rats was greater than vehicle-treated rats, however, the binding to membranes of hypothalamus in the two treatment groups did not differ. The binding of 3H-DSTLE in amygdala and hypothalamus of methimazole-treated rats did not differ but it was significantly greater in pons and medulla, midbrain, cortex and striatum of methimazole-treated rats than vehicle-treated rats. The binding of 3H-EKC to membranes of pons and medulla was lower and of striatum and cortex of methimazole-treated rats was significantly greater than vehicle-treated rats, but the binding to membranes of amygdala, hypothalamus, and midbrain of the two treatment groups did not differ. The results indicate that brain, mu-, delta- and kappa-opioid receptors are differentially altered in hypothyroidism.

Animals↗

Effect of acute cocaine administration on the cholinergic enzyme levels of specific brain regions in the rat.

Adult male Sprague-Dawley rats weighing between 170 and 204 g and maintained under controlled lighting and temperature conditions were used in this experiment. One group of animals was treated with 30 mg/kg of cocaine hydrochloride and the other group with saline. Rats were decapitated 20 min after cocaine injection and their brains were removed and the different regions including the medulla, pons, midbrain, cerebellum, hypothalamus, thalamus, hippocampus, and the cortex were dissected. All brain regions were assayed for choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities. The results obtained indicated that the administration of cocaine was associated with significant increases (p less than 0.01) in AChE activity in the medulla, pons, midbrain, hypothalamus, thalamus, and also in the hippocampus (p less than 0.05). A significant decrease in ChAT activity was found in the pons (p less than 0.01), hypothalamus, and thalamus (p less than 0.05), while a significant increase in ChAT activity was found in the cortex (p less than 0.05). The results suggest that the changes in general activity followed by stereotypic behavior may be related to the changes in the levels of cholinergic enzymes in specific brain regions.

Acetylcholinesterase↗

Binding of 3H-D-Pen2-D-Pen5-enkephalin to brain regions and spinal cord membranes of spontaneously hypertensive and normotensive Wistar-Kyoto rats.

The binding of 3H-D-Pen2-D-Pen5-enkephalin (DPDPE), a highly selective delta-opiate receptor agonist, to membranes of discrete brain regions and spinal cord of 10-week-old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined. The brain regions examined were amygdala, hippocampus, hypothalamus, pons and medulla, corpus striatum, midbrain and cortex. 3H-DPDPE bound to membranes of brain regions and spinal cord at a single high affinity site with apparent dissociation constant value of 4 nmol/l, except in cortex where the values were higher. The highest density of 3H-DPDPE binding sites were in hypothalamus and lowest in pons and medulla. The receptor density (Bmax value) and apparent dissociation constant (Kd value) of 3H-DPDPE to bind to delta-opiate receptors on the membranes of hippocampus, hypothalamus, corpus striatum, midbrain, cortex, pons and medulla and spinal cord of WKY and SHR rats did not differ. The Bmax value of 3H-DPDPE in amygdala of SHR rats was higher than in WKY rats, but the Kd values in the two strains did not differ. It is concluded that SHR rats have a higher density of delta-opiate receptors, labeled with 3H-DPDPE, in amygdala in comparison with WKY rats. Whether such a difference in the density of delta-opiate receptors is related to the elevated blood pressure of SHR rats is not clear.

Animals↗

Nitric oxide synthase activity in brain regions and spinal cord of mice and rats: kinetic analysis.

Nitric oxide synthase (NOS) activity was determined by the rate of conversion of [3H]arginine to [3H]citrulline in brain regions (midbrain, hypothalamus, cerebellum, hippocampus, corpus striatum, cortex, pons-medulla and amygdala) and spinal cord of male Swiss Webster mice and male Sprague-Dawley rats. In mice, high activity of NOS was found in cerebellum, hypothalamus and midbrain; intermediate activity in pons-medulla, hippocampus, amygdala, corpus striatum and cortex; and low activity in the spinal cord. In rat, highest activity of NOS was observed in cerebellum followed in decreasing order by midbrain, hypothalamus, cortex, striatum, pons-medulla, hippocampus and spinal cord. In all tissues, NOS activity was higher in rat than in mouse. Analysis of the Eadie-Hofstee plot indicated that the Vmax and Km values of the enzyme in cortex and cerebellum of rats were higher than in mouse tissues. These studies show differential distribution of NOS activity in mouse and rat brain regions and spinal cord and higher activity of NOS in rat brain regions and spinal cord compared to mouse tissues.

Amino Acid Oxidoreductases↗

Effects of aging and chronic hypertension on cerebral blood flow and cerebrovascular CO2 reactivity in the rat.

We measured regional cerebral blood flow (rCBF) in young and old Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats by a minimally invasive microsphere technique. Blood flows to the cerebrum, diencephalon, mesencephalon, cerebellum and pons-medulla during normocapnia were determined. To test the ability of the vessels to dilate, rCBF was also measured during hypercapnia. Reactivity to CO2 was calculated as delta rCBF/delta paCO2. In the old SHR, blood flow to the pons-medulla (88 +/- 8 ml/min/100 g, mean +/- SEM) was markedly lower than that in the young SHR (107 +/- 4 ml/min/100 g, p < 0.05), whereas the difference of those values in the old and young WKY rats was slight (0.05 < p < 0.1). There were no differences in the values of blood flow to the cerebrum, diencephalon, mesencephalon or cerebellum between the young and old rats in both species. Cerebrovascular CO2 reactivity was markedly impaired in the old SHR (p < 0.05) compared to that in the young SHR, but the difference in reactivity in the WKY rats was not significant. The results indicate that blood flow to the pons-medulla is reduced in association with age, particularly in the hypertensive animals, and that the ability of the cerebral vessels to dilate is impaired homogeneously by the combination of chronic hypertension and aging.

Aging↗

Multiple genetic determinants of variation of plasma lipoproteins in Alberta Hutterites.

We hypothesized that variation of nine candidate genes in lipoprotein metabolism would be associated with variation in fasting plasma lipoprotein variables in 718 Alberta Hutterites, a genetic isolate. We measured plasma lipids, lipoproteins, and apolipoproteins and analyzed DNA for genotypes of apolipoprotein (apo) B (APOB), paraoxonase (PON), lipoprotein lipase (LPL), VLDL receptor (VLDLR), apo CIII (APOC3), LDL receptor-related protein (LRP), hepatic lipase (HL), LDL receptor (LDLR), and apo E (APOE). Using a multivariate analysis, we found that (1) genotypes of APOB, PON, LPL, LDLR, and APOE were significantly associated with variation of plasma apo B-related traits; (2) genotypes of PON, LPL, and APOC3 were significantly associated with variation in plasma triglycerides; and (3) genotypes of VLDLR, APOC3, LDLR, and APOE were significantly associated with variation in plasma apo AI and HDL cholesterol. Regression analysis showed that between 3.2% and 7.8% of the total variation in plasma lipoproteins was accounted for by variation in the candidate genes tested. The observations demonstrate a modest but significant genetic component of variation in plasma lipoprotein levels that is due to the candidate genes studied in this normolipemic human genetic isolate.

Alberta↗

Genetic polymorphism of paraoxonase and the risk of coronary heart disease.

Recent studies have implicated paraoxonase, an HDL-associated enzyme, in providing protection against LDL oxidation, thus affecting the risk of coronary heart disease (CHD) in the general population. In this study, we evaluated the distribution of a biallelic PON polymorphism at codon 192 (A and B alleles) and its relationship with plasma lipids and CHD in two racial groups comprising Asian Indians and Chinese from Singapore. The frequency of the B allele was significantly higher in Chinese control subjects than in Indian control subjects (0.58 versus 0.33; P < .0001). With the exception of a marginal effect on apolipoprotein A-I levels in Indians, no other significant association was observed between the PON polymorphism and quantitative lipid traits in either racial group. However, there was a race-specific association of the B allele with CHD in Indians but not in Chinese. The Indian CHD patients had a significantly higher frequency of the B allele than control subjects (.43 versus .33; P = .014). The age- and sex-adjusted odds ratio for developing CHD with the B allele (BB+AB genotypes) was 2.01 (95% CI, 1.17 to 3.45; P = .011) compared with the A allele (AA genotype). When the Indian patients were stratified into subgroups, the association remained significant in nondiabetic patients (odds ratio, 2.29; P = .008), and it became stronger in patients with myocardial infarction (odds ratio, 2.94; P = .004) than in patients without myocardial infarction (odds ratio, 1.11; P = .76). These data indicate that a common polymorphism in the PON gene is an independent risk factor for CHD in populations with white ancestry.

Adult↗

Low molecular weight iron in cerebral ischemic acidosis in vivo.

BACKGROUND AND PURPOSE: Iron-catalyzed radical generation is a potentially significant mechanism by which extensive tissue acidosis exacerbates brain injury during ischemia/reperfusion. We hypothesized that levels of low-molecular-weight (LMW) iron increase during in vivo global cerebral ischemia in a pH-dependent manner, potentially catalyzing oxidant injury. The present study quantified regional differences in LMW iron during global cerebral incomplete ischemia and determined whether augmenting the fall in ischemic tissue pH with hyperglycemia also amplifies free iron availability. METHODS: Dogs anesthetized with pentobarbital-fentanyl were treated with 30 minutes of global incomplete cerebral ischemia produced by intracranial pressure elevation. Cerebral energy metabolites (ATP, phosphocreatine) and intracellular pH (pHi) were measured by 31P magnetic resonance spectroscopy. Preischemic plasma glucose level was manipulated to titrate end-ischemic pHi. After ischemia, brains were perfused with cold phosphate-buffered saline solution; then 16 different brain areas were sampled, filtered to separate the LMW fraction (<30000 D), and assayed by rapid colorimetric assay for tissue iron. Total iron, LMW iron, and protein in each sample were measured in sham-operated (no ischemia, n=8), normoglycemic ischemia (ISCH [glucose 7+/-4 mmol/L], n=7), and hyperglycemic (GLU-ISCH [glucose 31+/-3 mmol/L], n=9) groups. RESULTS: High-energy phosphates fell to near zero values in both ISCH and GLU-ISCH groups by 30 minutes but remained unchanged in the sham-operated group. As expected, pHi decreased during ischemia but to a greater extent in GLU-ISCH (6.20+/-0.05 in ISCH, 6.08+/-0.04 in GLU-ISCH, P<.05). Iron could be detected in all areas of the brain in sham-operated animals, with the highest amounts obtained from subcortical areas such as the hippocampus, pons, midbrain, and medulla. Total iron was higher in ISCH relative to sham-operated animals and higher in cortex and pons relative to GLU-ISCH. Regional LMW (as a percentage of total iron; LMW/total iron) was elevated in numerous brain areas in ISCH, including cortical gray matter, cerebellum, hippocampus, caudate, and midbrain. LMW/total iron was higher in GLU-ISCH versus ISCH in cortical gray matter only. In other brain areas, ischemic LMW/total iron was equivalent in glucose-treated or normoglycemic animals (white matter, thalamus, pons, medulla) or lower in the glucose-treated group (cerebellum, hippocampus, caudate, midbrain). CONCLUSIONS: These data demonstrate that levels of total and LMW iron increase with global cerebral ischemia in the majority of cortical and subcortical regions of normoglycemic brain. However, exacerbation of ischemic acidosis via glucose administration does not increase tissue iron and produces a greater increase in the LMW fraction in cortical gray matter only. In other brain regions, total and LMW iron availability is similar to that of nonischemic animals.

Acidosis↗

Changes in selected brain neurotransmitters and their metabolites in the lamb after thyroidectomy during the last two trimesters of gestation or the early neonatal period.

To evaluate in a development context the effect of congenital hypothyroidism on concentrations of the neurotransmitters norepinephrine, dopamine, and serotonin (5HT) in selected brain areas of the ovine fetus, we studied the effect of thyroidectomy at three ages on the concentrations of these neurotransmitters and their major metabolites, homovanillic acid and 5-hydroxyindoleacetic acid. Fetuses underwent thyroidectomy at 90-95 or 105-115 d gestation (term = 147-150 d) or 1-5 d after birth. Approximately 25 d after thyroidectomy, at d 120-125 or 130-135 of gestation or 25-30 d after birth, respectively, the ewes were killed and fetal brains removed. Neurotransmitters and their metabolites were measured by HPLC with electrochemical detection. Thyroidectomy in the 2nd trimester increased 5HT in five brain areas: anterior hypothalamus, dorsal medial hypothalamus, pons, medulla, and cerebellum. Thyroidectomy in the 3rd trimester increased 5HT in the pons and medulla, increased norepinephrine in the dorsal medial hypothalamus and pons, and increased homovanillic acid in the posterior hypothalamus. Thyroidectomy in the newborn period decreased NE in the anterior hypothalamus, ventral medial hypothalamus, and midbrain, decreased 5-hydroxyindoleactic acid in the posterior hypothalamus, lateral hypothalamus, dorsal medial hypothalamus, and ventral medial hypothalamus, and decreased homovanillic acid in the dorsal medial hypothalamus and ventral medial hypothalamus. From these data we conclude the following: 1) Hypothyroidism causes changes in neurotransmitter concentrations only in selected brain areas of the ovine fetus, rather than causing generalized and similar changes in all brain areas; and 2) 5HT 5-hydroxyindoleacetic acid concentrations are affected more often than the other neurotransmitters evaluated, perhaps because the 5HT neurotransmitter system is developing at these times.

Animals↗

Inhibitory and facilitatory areas of the ventral midbrain mediating release of corticotropin in the cat.

To examine the role of the ventral midbrain in the control of release of ACTH, we stimulated electrically 92 sites in the mesencephalon of 15 cats anesthetized with chloralose/urethane. Responses of arterial pressure could not account for change of release of ACTH. Three active areas were identified. First, in a dorsal facilitatory area that includes the dorsal longitudinal fasciculus, electrical stimulation led to changes in ACTH of +106, +117, and +90 pg/ml at 1.5, 3.5, and 6.5 min, respectively (P less than 0.05). Second, in a more ventral inhibitory area that includes the mammillary peduncle, electrical stimulation led to changes in ACTH of -63, -72, and -47 pg/ml, respectively (P less than 0.05). Third, in a ventral facilitatory area that includes the ventral tegmental area of Tsai, electrical stimulation led to changes in ACTH of +57, +56, and +59 pg/ml, respectively (P less than 0.01). The inhibitory and facilitatory areas of the ventral midbrain appeared to be continuous, respectively, with the inhibitory and facilitatory areas mediating control of ACTH in the dorsal rostral pons and in the hypothalamus. Anatomical evidence indicates projections from these ACTH-active areas of the midbrain and of the pons to ACTH-active areas of the hypothalamus. Thus, the present results suggest that the midbrain areas identified may represent pathways from ACTH-active areas of the pons to the hypothalamus.

Adrenocorticotropic Hormone↗

Internuclear ophthalmoplegia as an isolated or predominant symptom of brainstem infarction.

OBJECTIVE: To describe the clinical features, MRI findings, and pathogenesis of strokes producing internuclear ophthalmoplegia (INO) as an isolated or predominant clinical manifestation. METHODS: Thirty patients presenting with INO without (n = 12) or with (n = 18) minimal other neurologic signs were studied. MRI and angiogram (conventional in 3, MR angiogram in 27) studies were performed in all of them. RESULTS: Twenty-four presented with INO, whereas six initially presented with one-and-a-half syndrome that changed into INO. Dorsal brainstem infarcts responsible for the INO were located in the caudal pons in 4, rostral pons in 8, rostral pons and isthmus in 2, isthmus area in 14, isthmus and midbrain in 1, and midbrain in 1 patient. Vascular lesions were found in the posterior circulation in 14 patients (47%): at the basilar artery (BA) in 4, superior cerebellar artery (SCA) in 4, posterior cerebral artery (PCA) in 4, and both the PCA and the SCA in 1. The INO eventually disappeared in all patients, tending to last longer (p = 0.05) when it was associated with other neurologic signs. CONCLUSIONS: Isolated or predominant INO is a unique clinical stroke syndrome caused by small dorsal brainstem infarction. The pathogenesis, however, is heterogeneous, including distal occlusion of small penetrating arteries, atheromatous branch occlusion from the BA, SCA, or PCA, or major BA occlusion. The functional prognosis of these patients is excellent, although the INO tends to last longer when there are other neurologic deficits.

Adult↗

Genetic variants of the paraoxonases (PON1 and PON2) in the Chilean population.

We estimated the frequencies of PON1 and PON2 variants (linked genes) in two hospital samples taken from the northern (San José Hospital, SJH) and eastern (Clínica Las Condes, CLC) parts of Santiago, Chile, using the polymerase chain reaction followed by restriction endonuclease digestion. The two hospital samples have different degrees of Amerindian admixture (SJH, 34.5%; CLC, 15.9%), which is reflected in the observed frequencies of the PON1 *B allele (SJH, 43.1%; CLC, 33.7%) and the PON2*S allele (SJH, 86.3%; CLC, 77.6%); both allele frequencies are significantly different between samples. The frequencies of the combined PON1-PON2 genotypes *A/*B-*C/*C, *A/*B-*S/*S, and *B/*B-*S/*S and of the haplotypes PON*A,C and PON*B,S were significantly different between the SJH and CLC groups. None of the genotype frequencies deviated significantly from those predicted by the Hardy-Weinberg equation. No linkage disequilibrium was found between the PON1 alleles and any of the PON2 alleles in either group (all p > 0.05). In our samples 38.52% (SJH) and 26.25% (CLC) of chromosomes must have the haplotype PON*B,S, presumed to be related to the risk of coronary artery disease. Twenty-four of 193 (12.4%) SJH individuals and 7 of 122 (5.7%) CLC individuals were homozygotes for this haplotype. Finally, our data indicate ethnic-group-dependent genetic differences in the vulnerability to toxic organophosphorus.

Alleles↗