Sonographic determination of normal Conus Medullaris level and ascent in early infancy.

INTRODUCTION: Controversial reports exist in the literature regarding both the spinal level of the conus medullaris (CM) in normal infants and the age at which the CM achieves its adult level. Autopsy studies have demonstrated ascent continuing into early infancy while more recent imaging study series' suggest the adult conus level is attained by the 40th postmenstrual week. METHODS: The authors conducted a retrospective review of 1,273 screening lumbar ultrasound studies performed over 5 years at a pediatric tertiary referral center. All patients were infants referred for initial imaging to rule out the presence of a tethered spinal cord. Referral sources included urban academic, urban private practice, and rural private practice pediatricians. After excluding studies lacking sufficient documentation (n = 90) and those reported as abnormal (n = 106), 1,077 remained for review. The CM level and patient age in days were recorded from each study. Statistical analysis was performed using unpaired t testing and ANOVA for continuous variables; chi-square for categorical data. RESULTS: The mean CM level for infants in group I (ages 0-30 days) was compared to those in groups II (31-60 days) and group III (61-100 days). Group I had a mean CM level of 0.125 and 0.2 vertebral segments lower than groups II and III (p = 0.0005 and <0.0001, respectively). ANOVA comparison of all three groups confirmed a rostral migratory trend (p < 0.001). The prevalence of CM level caudal to L2 in group I was 13 %, group II 11.4 %, and group III 4.7 %; also indicating a significant rostral trend (p = 0.004). CONCLUSIONS: Rostral migration of CM level continues through the first few months of post-natal life, albeit of limited extent. Documentation of continued ascent in a neonate may obviate the need for magnetic resonance imaging.

Delayed profound local brain hypothermia markedly reduces interleukin-1beta gene expression and vasogenic edema development in a porcine model of intracerebral hemorrhage.

White matter (lobar) intracerebral hemorrhage (ICH) can cause edema-related deaths and life-long morbidity. In our porcine model, ICH induces oxidative stress, acute interstitial and delayed vasogenic edema, and up-regulates interleukin-1beta (IL-1beta), a proinflammatory cytokine-linked to blood-brain barrier (BBB) opening. In brain injury models, hypothermia reduces inflammatory cytokine production and protects the BBB. Clinically, however, hypothermia for stroke treatment using surface and systemic approaches can be challenging. We tested the hypothesis that an alternative approach, i.e., local brain cooling using the ChillerPad System, would reduce IL-1beta gene expression and vasogenic edema development even if initiated several hours after ICH. We infused autologous whole blood (3.0 mL) into the frontal hemispheric white matter of 20 kg pentobarbital-anesthetized pigs. At 3 hours post-ICH, we performed a craniotomy for epidural placement of the ChillerPad. Chilled saline was then circulated through the pad for 12 hours to induce profound local hypothermia (14 degrees C brain surface temperature). We froze brains in situ at 16 hours after ICH induction, sampled perihematomal white matter, extracted RNA, and performed real-time RT-PCR. Local brain cooling markedly reduced both IL-1beta RNA levels and vasogenic edema. These robust results support the potential for local brain cooling to protect the BBB and reduce injury after ICH.

Analysis of uroliths from cats and dogs in New Zealand, 1993-96.

AIMS: Canine and feline uroliths were analysed to determine the prevalence of particular types of urolith and the dog breeds at risk. METHODS: Three hundred and sixty-nine uroliths recovered from 316 dogs and 53 cats between November 1993 and December 1996 were analysed by X-ray diffraction, and by infrared spectrometry where X-ray diffraction alone was non-diagnostic. RESULTS: Bitches of small breeds especially Welsh corgi and Bichon frise, were most frequently affected. Struvite was the most common urolith (204 dogs). Oxalate (60 dogs) was the second most prevalent urolith identified, followed by cystine (24 dogs). The breeds producing cystine calculi were: Dalmatian, Bassett hound, Borzoi, Newfoundland, Shetland sheepdog, Labrador, Chihuahua, Fox terrier, English bulldog, Bichon frise, Doberman pinscher, Border collie. Silica uroliths were identified for the first time in New Zealand. All feline uroliths were struvite. CONCLUSION: The results are useful in determining the prevalence of specific types of urolith in New Zealand and the breeds at risk of forming them.

A review of the expanding field of exotic animal oral health care--veterinary dentistry.

This article reviews the clinical literature of the field of Veterinary Dentistry from its conception in the late 1960's to its rapidly expanding role today as an emerging clinical specialty practice in veterinary medicine. It defines eight dental sub-disciplines in contemporary veterinary oral health care from a practical point of view and provides information concerning standardization of key words searches, definition of terms, and use of the expanded Medical Subject Headings (MeSH) necessary for a comprehensive review of the rapidly expanding literature stored in electronic databases.

Beta-adrenergic receptor subtypes in human pineal gland.

The secretion of melatonin by the pineal has been promoted as a direct monitor of adrenergic function in depressive illness. However, discrepant findings have been reported, possibly reflecting a complex adrenergic regulation of pineal output. In order to clarify the anatomical localization and relative density of beta-adrenergic receptors and their subtypes in human pineal, quantitative autoradiographic analysis was conducted of beta-adrenergic receptors in postmortem specimens using the high affinity radioligand 125I-pindolol. Dense specific binding was found throughout the gland. beta 1 -adrenergic receptors were more numerous, but beta 2-receptors were present in an overlapping anatomical distribution with beta 1-receptors.

Liposome-entrapped PGE1 posttreatment decreases IL-1 alpha-induced neutrophil accumulation and lung leak in rats.

We found that treatment with liposome-entrapped prostaglandin E1 (Lip-PGE1), but not with empty liposomes and/or free PGE1, decreased the leak of intravascularly administered 125I-labeled albumin into lungs of rats given interleukin-1 alpha (IL-1 alpha) intratracheally. Lip-PGE1 treatment also decreased lung myeloperoxidase activity, lung lavage neutrophil increases, and lung histological abnormalities found in rats given IL-1 alpha intratracheally. Interestingly, decreased lung leak and lung neutrophil accumulation occurred when Lip-PGE1 was given intravenously 2.5 h after, but not immediately before, intratracheal IL-1 alpha administration. When Lip-PGE1 treatment was given both before and 2.5 h after IL-1 alpha administration, lung leak was decreased to baseline levels. Lip-PGE1 treatment given 2.5 h after IL-1 alpha administration also decreased lung oxidized glutathione levels, which increased in rats given IL-1 alpha intratracheally. We conclude that postinsult treatment with Lip-PGE1 decreases lung leak, neutrophil recruitment, and oxidative responses in lungs of rats given IL-1 alpha intratracheally.

Interleukin-1-induced lung neutrophil accumulation and oxygen metabolite-mediated lung leak in rats.

We found that intratracheal administration of recombinant interleukin-1 alpha (IL-1) into rats rapidly (< 5 h) increased neutrophils in lung lavages and caused an acute edematous lung injury which was reflected by lung albumin accumulation (lung leak) and histological abnormalities (perivascular cuffing). These IL-1-dependent processes were inhibited by prior administration of recombinant IL-1 receptor antagonist and did not occur following administration of heated IL-1. Several lines of evidence suggested that neutrophil-derived oxygen metabolites contributed to lung leak. First, lung leak did not occur in rats rendered neutropenic by vinblastine treatment 4 days before IL-1 administration but did occur in neutrophil-replete rats given vinblastine 1 day before IL-1 administration and control rats given IL-1. Second, treatment with a hydroxyl radical scavenger, dimethyl sulfoxide (DMSO) or a superoxide anion scavenger, manganese superoxide dismutase, decreased lung leak, lung lavage neutrophils, and histological abnormalities in rats given IL-1 intratracheally. Third, intratracheal IL-1 administration increased lung oxidized glutathione (GSSG) levels and expired H2O2 concentrations, and these two indices of oxidative stress were decreased by dimethyl sulfoxide or manganese superoxide dismutase treatment. We conclude that intratracheal administration of IL-1 increases neutrophils in the lung and causes a neutrophil and oxygen metabolite-dependent acute edematous lung injury.

[125I]RTI-55 binding to cocaine-sensitive dopaminergic and serotonergic uptake sites in the human brain.

[125I]RTI-55 is a newly synthesized cocaine congener that may offer advantages over other ligands previously used to examine cocaine binding sites. However, the in vitro pharmacological and anatomical characterization of [125I]RTI-55 binding sites has not been previously performed in human brain. To determine the specificity, stability, and feasibility of [125I]RTI-55 for use in radioligand binding assays in postmortem human tissue, a series of experiments were performed characterizing [125I]RTI-55 binding sites in human brain using homogenized membrane preparations and quantitative autoradiography. Analysis of the association, dissociation, and saturation data favored two-phase processes. A curve-fitting analysis of the data derived in saturation experiments found a high-affinity site with KD = 66 +/- 35 pM and Bmax = 13.2 +/- 10.1 pmol/g of tissue and a low-affinity site with KD = 1.52 +/- 0.55 nM and Bmax of 47.5 +/- 11.2 pmol/g of tissue. Competition by ligands known to bind to the dopamine transporter showed a rank order of RTI-55 > GBR-12909 > maxindol > WIN 35428 > = methylphenidate > (-)-cocaine > buproprion > (+)-amphetamine. Binding to serotonergic sites was evaluated in the midbrain. Results of the saturation experiment performed autoradiographically in the midbrain showed a single site with KD = 370 +/- 84 pM. It appears that [125I]RTI-55 should be useful in further studies of the regulation of cocaine binding sites using postmortem human specimens.

Cocaine use increases [3H]WIN 35428 binding sites in human striatum.

Animal studies suggest that chronic cocaine exposure may increase the function and/or synthesis of the dopamine transporter (DAT) under certain conditions, but the literature is complex. In order to test the hypothesis that cocaine exposure alters the DAT in humans, preliminary studies were done characterizing [3H]WIN 35428 binding in human striatum from normal controls. Following these experiments, the effects of chronic cocaine were examined in post mortem striatal specimens from 7 cocaine users and 7 controls matched for age and post mortem interval, employing quantitative autoradiography. Initial saturation experiments indicated that a one-site model was preferred with a Kd of 11 +/- 4 nM. [3H]WIN 35420 binding was then examined in cocaine users and controls at 0.5, 5, 10, and 50 nM radioligand concentrations. At each concentration of [3H]WIN 35420, optical densities for cocaine-exposed subjects were increased in caudate, putamen, and accumbens. The results suggest that total numbers of binding sites were increased in cocaine users. Based on the present and previous results, it appears that the regulation of the DAT is fairly plastic, and is highly sensitive to cocaine dosing regimes and withdrawal intervals. Chronic adaptations induced by cocaine in the DAT could contribute to the symptoms of binging, withdrawal depression, and/or craving.

Autoradiographic characterization of [3H]imipramine and [3H]citalopram binding in rat and human brain: species differences and relationships to serotonin innervation patterns.

The neuroanatomical distribution of binding sites for [3H]imipramine and [3H]citalopram was assessed by in vitro autoradiography in select regions of the rat and human forebrain. To determine involvement of serotonin-containing terminals in the binding of [3H]imipramine and [3H]citalopram, binding of these compounds was measured in rats after destroying serotonin-containing neurons with 5,7-dihydroxytryptamine (5,7-DHT). Treatment with this neurotoxin decreased serotonin content by 90% and reduced [3H]citalopram binding to a similar extent. These results demonstrate that [3H]citalopram binding is a reliable marker for serotonin-containing terminals. Binding of [3H]imipramine was reduced by only 15-35% after 5,7-DHT treatment. These latter results suggest that only a small fraction of [3H]imipramine binding to brain sections is associated with serotonergic terminals under standard conditions used in autoradiographic studies with the ligand. Dose-response effects of fluoxetine and desipramine on displacement of [3H]imipramine binding in forebrain regions indicate that the ligand labels predominantly high capacity, low affinity binding sites. To determine the utility of the rat brain as a model for [3H]imipramine and [3H]citalopram binding in the human brain, binding of the ligands was compared in human and rat hypothalamus, amygdala, and hippocampus. The pharmacological characteristics of [3H]imipramine and [3H]citalopram binding were similar in the rat and human brain. However, substantial species differences were observed in topographic patterns of [3H]imipramine binding within the hippocampus and hypothalamus. The distribution of [3H]citalopram binding sites within the amygdala and hypothalamus were also strikingly different in rats compared to humans. This work provides the first demonstration that marked species differences exist in the topography of serotonergic innervation and in the distribution of [3H]imipramine binding sites within the rat and human brain regions examined.

Beta-adrenergic receptor distribution in human and rat hippocampal formation: marked species differences.

The topography of beta-adrenergic receptors in the rat and human hippocampal formation was assessed by in vitro binding of 125I-pindolol to tissue sections. Marked differences were found in the distribution of beta-adrenergic receptors and in the relative amounts of beta 1 and beta 2 receptor subtypes in the two species. In the human, the highest receptor densities were present in the pyramidal cell layer and in the stratum lacunosum-moleculare. In the rat hippocampus, those regions contained the lowest densities of 125I-pindolol binding sites. The highest densities of beta-adrenergic receptors in the rat hippocampal formation were found in the ventral subiculum and in the entorhinal cortex. In contrast, in the human hippocampus, the subiculum and entorhinal cortex contained relatively low densities of the receptors. Competition studies with beta 1- and beta 2-selective antagonists revealed that beta 2-adrenergic receptors predominate in the human hippocampus and beta 1-adrenergic receptors predominate in the rat hippocampus. The marked species differences observed suggest that the pharmacological responsivity of the hippocampus to adrenergic agents and the role of noradrenaline in regulation of hippocampal function could be very different in rats compared to humans.

Evaluation of right ventricular and right atrial size in children with atrial septal defect using two-dimensional apex echocardiography.

The ability of two-dimensional apex echocardiography to evaluate right ventricular and right atrial size was evaluated in 43 normal children and compared with 20 patients with a secundum atrial septal defect. From the apical four chamber view, the long axis length and short axis diameter of the right ventricle and right atrium were measured. The end-diastolic area of the right ventricle and end-systolic area of the right atrium were determined by planimetry. These data were indexed for body surface area. When compared with normal subjects, the area index of the right atrium and right ventricle were enlarged significantly in patients with a secundum atrial septal defect (p less than 0.001 and p less than 0.001, respectively). Mean values for the short axis dimension of the right ventricle and for the short axis and long axis diameter of the right atrium were greater in atrial septal defect patients than in normal subjects (p less than 0.001 for all). However, when both groups were compared, considerable overlap existed between the dimension measurements. Right ventricular long axis length failed to separate the two groups. Thus, two-dimensional apex echocardiography provides a noninvasive means of assessing right ventricular and right atrial size in children with an atrial septal defect.

Modification of cardiopressor and respirogenic effects of doxapram by propranolol.

The respiratory stimulant doxapram hydrochloride has long been shunned in the United States because of a perpetuated fear of the alleged side effects of hypertension and tachycardia with attendant hypermetabolism and increased oxygen consumption. This study reports the results of the administration of doxapram alone, and of doxapram in conjunction with the beta-blocker propranolol on the blood pressure, heart rate, and respiratory rate of 12 healthy unanesthetized volunteer subjects. Results showed an augmentation in blood pressure (especially diastolic), a significant decrease in heart rate, and an unexpected actual increase in respiratory rate in the doxapram/propranolol group. Subtleties of sympathetic balance, as well as proposed future studies are discussed.

Serotyping of noncapsular Haemophilus influenzae.

A microtechnique is described for agglutination typing of Haemophilus influenzae. It also provides a further means for classification and study of noncapsular type-specific strains.

Selective culture medium to survey the incidence of Haemophilus species.

A culture medium for the selective isolation of Haemophilus species is described. Bacitracin and nutritional supplements were incorporated in a rich basal agar medium to which rabbit blood was added to distinguish hemolytic species. Colony counts of seven typed strains of H. influenzae on this medium were within practical limits of counts on other media tested for clinical use. The bacitracin medium was as reliable as hemoglobin-agar for detecting H. influenzae and more sensitive for detecting other Haemophilus species in a clinical survey with the advantage of selectivity.