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Biomedical subjects

S E Smith

Publications and source records attributed to S E Smith.

At least 73 records · Page 4Linked to original sources
PubMed1995

Pholedrine: a substitute for hydroxyamphetamine as a diagnostic eyedrop test in Horner's syndrome.

Mydriatic responses to eyedrops containing the indirect acting sympathomimetic amines tyramine, hydroxyamphetamine, and pholedrine have been compared in 10 healthy subjects. Pholedrine, the n-methyl derivative of hydroxyamphetamine, at a concentration of 1% had effects similar to those produced by 0.5% hydroxyamphetamine itself. Pretreatment with topical guanethidine attenuated its responses and in 13 patients with unilateral Horner's syndrome it distinguished clearly those five patients who had preganglionic from the eight with postganglionic lesions. It is concluded that 1% pholedrine may be substituted for 0.5% hydroxyamphetamine, which is no longer available, as a diagnostic agent for use in Horner's syndrome.

Adolescent↗
PubMed1995

Noradrenergic activity in rat brain during rapid eye movement sleep deprivation and rebound sleep.

Noradrenergic locus ceruleus neurons are most active during waking and least active during rapid eye movement (REM) sleep. We expected REM sleep deprivation (REMSD) to increase norepinephrine utilization and activate the tyrosine hydroxylase (TH) gene critical for norepinephrine production. Male Wistar rats were deprived of REM sleep with the platform method. Rats were decapitated after 8, 24, or 72 h on small (REMSD) or large (control) platforms or after 8 or 24 h of rebound sleep after 72 h of the platform treatment. During the first 24 h, norepinephrine concentration, measured by high-performance liquid chromatography/electrochemical detection, was lower in the neocortex, hippocampus, and posterior hypothalamus in REMSD rats than in large-platform controls. After 72 h of REMSD, TH mRNA, measured by in situ hybridization, was increased in the locus ceruleus and norepinephrine concentrations were increased. Polygraphy showed that small-platform treatment caused effective and selective REMSD. Serum corticosterone measurement by radioimmunoassay indicated that the differences found in norepinephrine and TH mRNA were not due to differences in stress between the treatments. The novel finding of sleep deprivation-specific increase in TH gene expression indicates an important mechanism of adjusting to sleep deprivation.

Animals↗
PubMed1995

Addition of carbonic anhydrase augments extracellular pH buffering in rat cerebral cortex.

1. The ability of the extracellular space to buffer rapid alkaline shifts was studied in rat cortex in vitro and in vivo. Alkaline shifts were generated by iontophoresis of OH- or were evoked by pressure ejection of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). 2. In cortical slices, alkaline shifts induced by OH- were enhanced by the carbonic anhydrase (CA) inhibitor benzolamide (83 +/- 16%, mean +/- SE), and were decreased by superfusion of 10 mg/l CA (-59 +/- 4%). CA had no effect at 1 mg/l, and no additional effect at 100 mg/l. 3. In slices, and in vivo, alkaline shifts induced by AMPA were similarly enhanced by benzolamide and decreased by superfusion of CA. 4. These data indicate that extracellular CA activity is less than that required for maximum buffering. This suggests that equilibrium between CO2 and bicarbonate may not be attained during rapid extracellular pH shifts.

Aging↗
PubMed1995

Cerebroprotective effect of lamotrigine after focal ischemia in rats.

BACKGROUND AND PURPOSE: Glutamate receptor antagonists are protective in animal models of focal cerebral ischemia. Lamotrigine (3,5-diamino-6-[2,3-dichlorophenyl]-1,2,4-triazine) is an anticonvulsant drug that blocks voltage-gated sodium channels and inhibits the ischemia-induced release of glutamate. We describe the cerebroprotective effect of lamotrigine (as the isethionate salt) after middle cerebral artery occlusion in rats. METHODS: Neurological deficit and infarct volume (visualized by the lack of reduction of 2,3,5-triphenyltetrazolium chloride) 24 hours after permanent left middle cerebral artery occlusion were studied in Fischer rats (n = 8 per group per dose). RESULTS: Lamotrigine at 20 mg/kg i.v. over 10 minutes administered immediately after middle cerebral artery occlusion reduced total infarct volume by 31% and cortical infarct volume by 52%. Lamotrigine at 8 mg/kg i.v. over 10 minutes reduced cortical infarct volume by 38%. Lamotrigine at 50 mg/kg i.v. for 10 minutes was not cerebroprotective and induced a decrease of 29 +/- 15 mm Hg in mean arterial blood pressure (P < .05, n = 8). The optimum dose of lamotrigine (20 mg/kg i.v. over 10 minutes) when administered with a 1-hour delay after middle cerebral artery occlusion reduced cortical infarct volume by 41%. Lamotrigine (20 mg/kg i.v. over 10 minutes) with a 2-hour delay after middle cerebral artery occlusion was ineffective. Neurological deficits after 24 hours were improved after immediate treatment with lamotrigine at 20 mg/kg i.v. over 10 minutes. CONCLUSIONS: The cerebroprotective effect of lamotrigine in rats is limited to a narrow dose range between 8 and 20 mg/kg. Lamotrigine or analogous compounds may be useful when given shortly after the onset of stroke.

Animals↗
PubMed1995

Intramedullary nailing of humeral shaft fractures.

Twenty-one patients with 22 acute traumatic fractures of the humeral diaphysis were treated either with the True/Flex intramedullary rod or the Russell-Taylor rod. Follow-up is provided on 20 fractures. Indications for fixation on all but 3 patients was either multiple fractures, associated chest or abdominal trauma, vascular interruption, or open fracture. The series included 4 open fractures. Time to union averaged 7.6 weeks, with two nonunions, both in open fractures. Two isolated preoperative radial nerve palsies resolved fully; four brachial plexus injuries had a more complex recovery. No iatrogenic nerve damage was encountered. Excluding those patients with brachial plexus deficits, shoulder range of motion returned reliably. Impingement with a rod prominence was noted in 1 fracture. Functionally, all of the fractures, aside from those associated with a brachial plexus injury, had a normal or only mildly limiting result as reported by the patient. Additionally, eight humeral nonunions were treated with a reamed Russell-Taylor humeral nail with supplemental iliac crest bone graft at the time of nailing in 3 patients. Five of these 8 patients went on to union.

Elbow Joint↗
PubMed1994

Calcium dependence of glutamate receptor-evoked alkaline shifts in hippocampus.

Glutamate receptor activation induces an extracellular alkalinization in rodent hippocampus. We studied its Ca2+ dependence and pharmacology in hippocampal slices. Glutamate-evoked alkaline shifts were blocked by 0 Ca2+ saline. Alkalinizations induced by AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) and NMDA (N-methyl-D-aspartate) were abolished by 20 microM CNQX (6-cyano-7-nitro-nitroquinoxaline-2,3-dione) and 50 microM APV (DL-2-amino-5-phosphonovalerate), respectively. The AMPA- and NMDA-evoked alkaline shifts were blocked by 0 Ca2+, however, AMPA-induced [K+]o elevation was unaffected. These data suggest that the glutamate receptor-channel does not mediate H+ influx, and support a role for Ca(2+)-H+ exchange.

Alkalies↗
PubMed1994

Local and commissural neuropeptide-containing projections of the nucleus of the solitary tract to the dorsal vagal complex in the pigeon.

The neuropeptide content of neurons of the nucleus of the solitary tract (NTS), which have local and commissural projections to the dorsal motor nucleus of the vagus (DMNX) and to NTS, were demonstrated in the pigeon (Columba livia) by using a combined fluorescein-bead retrograde-transport-immunofluorescence technique. The specific peptides studied were bombesin, cholecystokinin, enkephalin, galanin, neuropeptide Y, neurotensin, and substance P. Perikarya immunoreactive for bombesin were located in medial tier subnuclei of NTS and the caudal NTS. Most galanin- and substance P-immunoreactive cells were found in subnucleus medialis ventralis. Cells immunoreactive for neuropeptide Y were found in the medial tier of NTS and in the lateral tier, especially in subnucleus lateralis dorsalis intermedius. The majority of enkephalin- and neurotensin-immunoreactive cells were found centrally in subnuclei medialis dorsalis and medialis intermedius. Cells immunoreactive for cholecystokinin were located in subnuclei lateralis dorsalis pars anterior, medialis superficialis, and the caudal NTS. Based on the presence of retrogradely labeled cells, numerous neurons of the medial tier of NTS, but extremely few lateral tier NTS neurons, had projections to the ipsilateral and contralateral DMNX and NTS. The number of retrogradely labeled NTS cells was always greater ipsilaterally than contralaterally. The percentages of peptide-immunoreactive NTS cells that projected to the ipsilateral and contralateral DMNX were in the ranges of 29-61% and 10-48%, respectively. The percentages of peptide-immunoreactive NTS cells that projected to the contralateral NTS ranged from 13 to 60%. Peptide-immunoreactive NTS cells that have local and commissural projections to DMNX and NTS may act as interneurons in vagovagal reflex pathways and in the integration of visceral sensory and forebrain input to NTS and DMNX.

Animals↗
PubMed1994

An investigation of the origin of extracellular GABA in rat nucleus accumbens measured in vivo by microdialysis.

GABA transmission in the nucleus accumbens is believed to play a central role in motivational processes and the expression of psychostimulant drug action. Here we report measurements of extracellular GABA in nucleus accumbens of the rat and investigate its origin. Extracellular GABA was detected using microdialysis in combination with a novel HPLC-based assay. In the awake rat, GABA in the microdialysates (1) increased 10-fold following perfusion with 0.5 mM nipecotic acid, a GABA releasing agent and uptake blocker, (2) increased 7-fold following local perfusion with 50 mM KCl, (3) decreased 50% following perfusion with tetrodotoxin, (4) decreased 50% following perfusion with a Ca(2+(-free medium and (5) decreased 40% following perfusion with high (12.5 mM) MgCl. Finally, in the anaesthetized rat, GABA in the microdialysates decreased 50% following i.p. injection of 100 mg/kg 3-mercaptoproprionic acid, a GABA synthesis inhibitor. We conclude that GABA in microdialysates from nucleus accumbens of the rat (awake) responds appropriately to selected pharmacological agents and derives at least in part (50%) from neurones.

3-Mercaptopropionic Acid↗
PubMed1994

Isolation of two contigs of overlapping cosmids derived from human chromosomal band 3p21.1 and identification of 5 new 3p21.1 genes.

Consistent loss of DNA sequences from several regions on the short arm of human chromosome 3 has suggested that multiple tumor suppressor genes reside on chromosome 3p in various types of cancer cells. We have focused our efforts on an analysis of chromosomal band 3p21.1 since aminoacylase-1 (ACY1), which is localized to this band, has been shown to have lower levels of expression in several small cell and non-small cell lung cancer cell lines. Starting with two cosmids within 3p21.1, D3S92 and D3S93, we have isolated two separate contigs of overlapping cosmids within 3p21.1, by screening a library of 5700 chromosome 3-specific cosmid clones. Detailed restriction maps for these two contigs show that they contain multiple clusters of rare cutting restriction endonuclease sites. One contig extends for 100 kb and encompassed both ACY1 and D3S92, and the other extends about 80 kb around the D3S93 locus. Many different restriction fragments derived from these two contigs were found to be evolutionarily conserved and hybridized to distinct message transcripts. These fragments were used to identify homologous cDNAs from an adenogastric cDNA library, and several of these cDNAs were partially sequenced. We have identified five new genes from these two contigs and there is evidence to suggest that several additional genes reside within these cosmid contigs. The genes identified from 3p21.1 were then hybridized to DNA, isolated from a series of lung cancer cell lines and matched normal and tumor DNA from lung cancer patients. No alterations were detected with any of these probes, both at the DNA or RNA levels. A similar analysis with DNA fragments derived from these two genomic regions also failed to detect any alterations.

Animals↗
PubMed1994

Identification of human chromosome region 3p14.2-21.3-specific YAC clones using Alu-PCR products from a radiation hybrid.

Deletion of DNA sequences from at least three different regions on the short arm of human chromosome 3 (3p13-14, 3p21 and 3p25) are frequently observed during the development of many solid tumors, including lung cancers and renal cell carcinomas. In order to physically characterize the 3p21 region, we previously identified a radiation fusion hybrid that contained about 20 megabases of DNA from chromosome region 3p14.2-p21.3. In this study total Alu-PCR products from this hybrid were used as a probe to isolate 86 yeast artificial chromosomes (YAC) clones from a 620-kb average insert YAC library (ICRF). Sixty-nine Alu-PCR markers, generated from the YACs, and seven PCR primers were used to screen for overlaps between individual clones. Seven contigs were identified encompassing 32 YAC clones. Based on previous information about localization of the PCR primers, the three largest contigs could be assigned to smaller subregions between 3p14.2 and 3p21.3. By this work a large proportion of the 3p14.2-21.3 region is covered with large-insert YAC clones.

Base Sequence↗
PubMed1994

Diurnal variation in pulsatile ocular blood flow in normal and glaucomatous eyes.

Ocular blood flow, in particular to the optic nerve head, is considered important in determining the extent of glaucomatous damage. The 24-hour variation in the pulsatile component of ocular blood flow (POBF) was measured using a pneumotonometer linked to the Langham Ocular Blood Flow System. Intraocular pressure (IOP), ocular pulse amplitude, POBF, systemic blood pressure and heart rate were recorded at three-hourly intervals over a 24-hour period in 10 ocular hypertensives, eight patients with primary open angle glaucoma (POAG) treated with timolol eyedrops (G timolol 0.25%), and eight ocular normotensive control subjects. The POAG subjects were readmitted for a second set of 24-hour measurements after temporarily discontinuing G timolol for two weeks. The POBF showed no significant diurnal variation in any of the patient groups, the POAG values being taken from the "off treatment" period. By contrast, there were overnight falls in IOP, ocular pulse amplitude, blood pressure and heart rate, which reached significance in some groups. This suggests that overall there are compensatory changes in IOP, blood pressure, heart rate, and perhaps ocular vascular resistance, to preserve POBF overnight. Within all groups there was much individual variation, with some subjects showing an overnight fall in POBF, suggesting a lack of autoregulation in these cases who might prove to be at greater risk of developing nocturnal glaucomatous damage. When timolol was withdrawn from POAG subjects, there was no change in POBF despite an increase in IOP, implying that timolol, though effective as ocular hypotensive, did not alter POBF.

Aged↗
PubMed1994

An appetitively conditioned taste elicits a preferential increase in mesolimbic dopamine release.

Rats were prepared with intragastric (IG) cannulae for infusing a nutrient into the stomach and microdialysis guide shafts in the nucleus accumbens (NAC) and striatum (STR) for measuring changes in extracellular dopamine. Prior to dialysis, subjects were trained to prefer the mildly bitter taste of sucrose octaacetate (SOA; CS+) by pairing voluntary intake with automatic IG infusions of nutritive polycose. The mildly sour taste of citric acid (CS-) was paired with IG water infusions as a control. Unconditioned animals received four exposures to SOA and citric acid on counterbalanced, alternating days. After training, dialysis samples were collected every 30 min before, during, and after intake of the CS+ or CS- in response to 14 h water deprivation on counterbalanced, consecutive days. Voluntary intake of the CS+ for 30 min significantly increased extracellular DA in the NAC but not in the STR of conditioned subjects. Intake of the CS- did not alter DA efflux at either site. Unconditioned, control rats also showed no DA response to either taste. These results show selective activation of the mesolimbic dopaminergic projection system as a consequence of a conditioned taste stimulus paired with a nutritive gastric load. This suggests that conditioned DA release may play a role in learned ingestive behavior based on the postingestive effects of food.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Prenatally detected posterior urethral valves: is gestational age at detection a predictor of outcome?

Between 1982 and 1992, 67 boys with posterior urethral valves were managed at our hospital, including 32 (48%) in whom the condition was detected prenatally. We examined the relationship between gestational age at detection and outcome at a median followup of 3.9 years (range 4 months to 10 years). Detection at or before 24 weeks of gestation predicted a poor outcome with 9 of 17 patients (53%) dead or in chronic renal failure at followup. Of the cases detected later in pregnancy only 1 had a poor outcome (p = 0.01). All of the cases detected after 24 weeks of gestation had had normal second trimester scans. Growth parameters for boys in the early and late detection groups were not statistically different. However, there was a significant association between renal failure and growth with 67% versus 14% having heights less than the 3rd percentile (p = 0.05). Respiratory distress at birth predicted a poor outcome, while the presence of palpable abdominal abnormalities or vesicoureteral reflux failed to predict outcome.

Female↗
PubMed1994

Clinical application of polymerase chain reaction amplification to diagnosis of herpes virus infection.

Amplification of viral DNA offers a potentially sensitive and specific method for identifying herpes viruses in pathologic specimens. The purpose of this study is to assess the value of polymerase chain reaction amplification of DNA as a diagnostic test for herpes virus in pathologic specimens. The purpose of this study is to assess for herpes virus infections. We examined 79 paraffin-embedded tissue samples from 43 patients and 55 viral culture samples from 45 patients. Herpes virus DNA in the specimens was amplified by polymerase chain reaction. Using paraffin-embedded tissue on which a diagnosis of herpes virus was made by morphologic criteria, 11 of 19 patients had herpes virus DNA identified by PCR; herpes virus DNA was not identified in any of 35 negative control specimens. Herpes virus DNA was also identified by polymerase chain reaction in all of the positive herpes virus culture specimens. Of 29 culture negative specimens, herpes virus DNA was identified in six. We conclude that polymerase chain reaction is useful to establish or confirm the presence of a herpes virus infection in paraffin-embedded tissue samples and that it is more sensitive than viral culture.

DNA, Viral↗
PubMed1994

Mild dilatation of the fetal kidney: a follow-up study.

OBJECTIVE: To assess morbidity in children with mild prenatally detected pelvicalyceal dilatation and to document the natural history of this ultrasound finding in post-natal life. PATIENTS AND METHODS: A retrospective (on-going) study was carried out in 29 children (39 kidneys) with mild dilatation confined to the pelvis and/or calices confirmed on initial post-natal ultrasound scan. Re-evaluation was carried out at a mean age of 4.2 years (range 1.5-7.8). Clinically, each patient's history, height, weight and blood pressure were recorded. On ultrasound examination the renal length, collecting system appearances and dimensions were recorded. RESULTS: Vesico-ureteric reflux was demonstrated in 1 of 14 infants who underwent neonatal micturating cystourethrography. During cumulative follow-up totaling 122 years, there were only two documented episodes of urological morbidity, i.e. one episode of unexplained haematuria and one of urinary tract infection. By a mean age of 4.2 years the ultrasound appearances had reverted to normal in 69% of kidneys. In 31% dilatation persisted and was unchanged or diminished in severity. No case of increasing dilatation was seen. Renal growth was normal in 97% of kidneys. CONCLUSIONS: Mild dilatation of the fetal urinary tract is a common prenatal ultrasound finding. When confined to the renal pelvis and/or calices it is of doubtful clinical significance and is associated with a low level of morbidity in infancy and early childhood. Invasive investigation in post-natal life is not justified.

Child↗
PubMed1994

Effects of a patent foramen ovale on arterial saturation during exercise and on cardiovascular responses to deep breathing, Valsalva manoeuvre, and passive tilt: relation to history of decompression illness in divers.

OBJECTIVE: To determine whether the presence of a patent foramen ovale could result in significant arterial desaturation and affect the responses of heart rate and blood pressure to physiological manoeuvres and to determine whether responses differed between those with and those without prior clinical events associated with a patent foramen ovale. DESIGN: Blind controlled study. SETTING: Teaching hospital. PATIENTS: Divers with a large patent foramen ovale shown by contrast echocardiography and divided into those who had neurological decompression illness that started within 30 minutes of surfacing (group 1), those who had no history of decompression illness (group 2), and age and sex matched control divers who had no evidence of intracardiac shunts (group 3). MAIN OUTCOME MEASURES: The change in percentage haemoglobin oxygen saturation during treadmill exercise and the response of heart rate and blood pressure to physiological manoeuvres. RESULTS: There were no significant differences between the three groups but two divers in group 1 showed clinically important desaturation during exercise and unusual blood pressure and heart rate responses to passive tilt. These divers were notable for having the greatest number of episodes and the most severe single episode of spinal cord decompression illness. CONCLUSION: A large patent foramen ovale may be associated with clinically significant arterial desaturation and unusual responses of heart rate and blood pressure in some healthy subjects.

Arteries↗