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Biomedical subjects

P Burns

Publications and source records attributed to P Burns.

At least 37 records · Page 2Linked to original sources

An fMRI study of stimulus equivalence.

In order to study brain activation during the formation of equivalence relations, 12 subjects underwent fMRI during matching-to-sample (MTS) tests of (1) previously trained arbitrary relationships between iconic stimuli and the untrained, emergent relations of (2) symmetry, (3) transitivity, and (4) symmetry with transitivity, plus a test of verbal fluency (VF). Brain activation was similar in all MTS tasks and in the VF task. In particular, both types of task activated dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex bilaterally. However VF, but not the MTS tasks, activated Broca's area. In three of the four MTS tasks, behavioural accuracy was significantly correlated with left lateralisation of DLPFC activity. Brain activation patterns during equivalence thus resembled those involved in semantic processing underlying language, without involving regions concerned with the simple sub-vocal articulation of stimulus names.

Adult↗

A meta-analysis of the use of typical antipsychotic agents in bipolar disorder.

BACKGROUND: The potential benefits of typical antipsychotic agents in bipolar disorder are offset by serious treatment-associated side effects. Despite these concerns and the availability of mood stabilizing agents, the treatment of bipolar disorder with typical antipsychotic agents appears to be widespread. METHODS: A Medline search identified 16 publications that outlined medication use among 2378 bipolar disorder patients. Meta-analysis was used to estimate a weighted average of the relative proportions of the treatment use, where the weights were the reciprocals of the estimated variances for each study. RESULTS: Overall, 84.7% of bipolar patients received typical antipsychotic agents, with a loading toward a greater in-patient (90.7%) relative to out-patient (65.3%) use. Monotherapy accounted for 53.8% of typical antipsychotic use, and typical antipsychotic/mood stabilizer combination therapy accounted for 47.4%. In four studies where length of treatment data were available, the median of minimum typical antipsychotic use was 2.5 months, with 96.0% of the patients receiving typical antipsychotic agents. LIMITATIONS: The meta-analytic technique employed in this analysis is limited by the possible inclusion of studies with unreliable study designs or biased treatment practices, publication bias in which some studies may not have been reported, and possible lack of identification of all relevant studies. CONCLUSIONS: Typical antipsychotic agents are commonly used in the treatment of bipolar disorder, possibly due to dissatisfaction with mood stabilizer monotherapy especially in psychotic mania, the high prevalence of psychotic symptoms in acute mania, inappropriate continuation of typical antipsychotic agents after initial stabilization, and/or unavailability or unfamiliarity with new treatments. These findings also suggest that typical antipsychotics may have not only antipsychotic effects in mania but perhaps also antimanic properties.

Antimanic Agents↗

Plasma choline in normal newborns, infants, toddlers, and in very-low-birth-weight neonates requiring total parenteral nutrition.

Choline deficiency is associated with hepatic abnormalities in adult volunteers and patients administered total parenteral nutrition (TPN). Preliminary investigation has suggested that plasma-free choline concentration (PFCh) is greater in neonatal animals, including humans, than in adults. The aims of this study were to determine the normal PFCh and phospholipid-bound choline concentration (PPLBCh) for newborns, infants, and toddlers and to determine the change during TPN. We also sought to determine the degree of fetal choline extraction, the relation between maternal and newborn plasma choline concentrations, and the relation between plasma choline status and normal newborn length, weight, and gestational age. Blood samples were obtained from 104 full-term newborns in two centers (Ben Taub and Maimonides), 25 mothers, 21 normal infants aged 20.3 +/- 11.8 wk, 12 normal infants aged 62.4 +/- 3.9 wk, and 14 preterm infants (gestational age = 28.9 +/- 2.2 wk) who required TPN. The vein PFChs were 28.1 +/- 13.0 nmol/mL (Ben Taub) and 68.1 +/- 16.9 nmol/mL (Maimonides). The artery PFChs were 27.1 +/- 13.0 nmol/mL (Ben Taub) and 57.9 +/- 11.6 nmol/mL (Maimonides). The vein PPLChs were 1004.7 +/- 246.6 nmol/mL (Ben Taub) and 1121.2 +/- 289.6 nmol/mL (Maimonides). The artery PPLChs were 1065.7 +/- 469.3 nmol/mL (Ben Taub) and 1106.9 +/- 285.8 nmol/mL (Maimonides). The vein-minus-artery differences for PFCh were 1.0 +/- 9.7 nmol/mL (Ben Taub) and 10.2 +/- 10.9 nmol/mL (Maimonides). The vein-minus-artery differences for PPLCh were -51.9 +/- 398.2 nmol/mL (Ben Taub General Hospital, Houston, Texas) and 14.4 +/- 254.3 nmol/mL (Maimonides, New York, New York). Maternal venous PFCh was 8.4 +/- 3.1 nmol/mL. Maternal venous PPLCh was 2592.1 +/- 584.0 nmol/mL (range = 1227.8-3729.0). Maternal venous PFCh correlated with newborn arterial PFCh (r = 0.53, P < 0.05) but not with newborn venous PFCh. No correlation was seen between maternal venous and newborn PPLCh. No significant differences were seen in PPLCh or choline extraction in Ben Taub versus Maimonides patients, although PFCh was significantly greater in the newborns from Maimonides (P < 0.05). The mean venous PFCh and PPLCh in the preterm infants before beginning TPN was 21.2 +/- 6.3 and 1366.8 +/- 339.1 nmol/mL, respectively. Just before initiation of tube feeding (4.0 +/- 2.7 d after TPN had been started), mean venous PFCh and PPLCh was 18.4 +/- 5.3 and 2251.8 +/- 686.9 nmol/mL, respectively. When TPN was discontinued and tube feeding increased to goal, after 10.8 +/- 10.4 d, venous PFCh and PPLCh was 22.6 +/- 8.7 and 2072.5 +/- 540.6 nmol/mL, respectively. Venous PFCh and PPLCh was 13.4 +/- 2.5 and 1827.5 +/- 327.0 nmol/mL, respectively in the older infant group. In conclusion, newborn PFCh is significantly greater than PFCh in adults but falls to adult levels within the first year of life. Low maternal PFCh may be associated with low newborn PFCh. Normal newborn plasma choline status has no bearing on intrauterine growth, although the role of maternal choline deficiency in underweight newborns is unknown. Newborn PPLCh is substantially below that of adults, which suggests its use in membrane synthesis during growth.

Adult↗

Cerebral Na concentration, Na appetite and thirst of sheep: influence of somatostatin and losartan.

Na and water intakes of Na-depleted sheep are influenced by changes in cerebral Na concentration. The effect of intracerebroventricular infusion of somatostatin or losartan, the ANG II type 1 receptor antagonist, on the Na appetite and thirst of Na-depleted sheep during infusions that decrease (intracerebroventricular hypertonic mannitol) or increase (intracerebroventricular or systemic hypertonic NaCl) cerebral Na concentration was investigated. Na intake was increased but water intake was unchanged during intracerebroventricular infusion of hypertonic mannitol. The increased Na appetite caused by intracerebroventricular infusion of hypertonic mannitol was decreased by concurrent intracerebroventricular infusion of either somatostatin or losartan, with somatostatin being most effective. Water intake was increased during intracerebroventricular infusion of hypertonic mannitol and somatostatin. Na intake was decreased and water intake was increased during systemic or intracerebroventricular infusion of hypertonic NaCl. Intracerebroventricular infusion of losartan blocked both (Na and water intake), whereas somatostatin did not influence either of these changes in intake. The results further consolidate a role for somatostatin and ANG II in the central mechanisms controlling Na appetite and thirst of sheep.

Angiotensin II↗

Phase I chemotherapy study of biochemical modulation of folinic acid and fluorouracil by gemcitabine in patients with solid tumor malignancies.

PURPOSE: This phase I biochemical modulation study evaluated the maximum-tolerated dose (MTD), toxicity, and effectiveness of the combination of folinic acid (FA)/fluorouracil (5-FU) followed by escalated dose levels of gemcitabine (FFG) in patients with advanced solid tumors. PATIENTS AND METHODS: Patients were refractory to primary treatment and/or without effective treatment options. Twenty-eight patients received an intravenous (IV) infusion of FA 100 mg/m(2) over 1 hour and a 5-FU 450 mg/m(2) IV bolus in the middle of the FA infusion. After the FA infusion, gemcitabine was administered at a steady rate of infusion of 10 mg/m(2)/min over initially 30 minutes and with increases of an additional 15 minutes at each given level. One cycle consisted of six weekly treatments followed by a 2-week rest. RESULTS: The MTD of gemcitabine was established at 900 mg/m(2) given over 90 minutes. Eight patients of 21 with metastatic colorectal cancer achieved responses (one complete response; seven partial responses), for a response rate of 38%. Responses were seen across the gemcitabine doses of 300 to 900 mg/m(2). One patient had prior treatment with FA/5-FU for advanced disease. Patients with colorectal carcinoma had a median survival of 18 months, and the patient with lung carcinoma has been alive for 24+ months. CONCLUSION: The combination chemotherapy of FFG was well tolerated and may benefit patients with advanced colorectal carcinoma. A phase II evaluation in this patient population is in progress.

Adult↗

'of Mice and men' (John steinbeck)-How do we determine the potential for immunotoxicity in humans?

PURPOSE: Immunotoxicology is most simply defined as the study of adverse effects on the immune system resulting from exposure to drugs, environmental and industrial chemicals, and in some instances, biological materials. The science of immunotoxicology has validated animal models to conduct risk assessment. However, approaches to characterize immunotoxicity in humans are poorly defined. Animal models have indicated that a primary immune response is most predictive of immunotoxicity. Because vaccines can trigger a primary immune response, this approach may have utility in humans. The purpose of this project was to determine if the response to the influenza vaccine can be validated as an objective measurement of immune status in the workplace.METHODS: We randomly selected employees to receive the influenza vaccine and employees, matched according to age and gender, to receive the placebo. The participants (32 test group and 19 placebo group) completed a brief questionnaire to identify potential confounding factors. Specific anti-influenza antibodies were measured in the serum via an ELISA 30 days after administering the vaccine or placebo.RESULTS: Only 50% (16 of 32 subjects) produced a positive response which is defined by the Centers for Disease Control as a four-fold increase in serum titers. Not unexpectedly, all samples contained antibody to influenza prior to vaccination, and a number of the participants who did not achieve a positive response started with high serum titers.CONCLUSIONS: The influenza vaccine was originally selected for this study because of costs, acceptability to the population and proven safety and efficacy. However, the results of the present investigation suggest that this approach will have little utility as a workplace monitor of human immunotoxicity because most individuals would not be making a primary antibody response. Other technical limitations with the influenza vaccine will be presented; and the alternatives for other biomonitors of human immunotoxicity will be discussed.

Journal Article↗

The inhibitory effect of hormones associated with stress on Na appetite of sheep.

Stress is a large stimulus of Na appetite in rabbits, rats, and mice. This study investigated the influence of some peptides implicated in stress, i.e., adrenocorticotropin (ACTH), corticotropin-releasing factor (CRF), and the recently discovered member of the CRF family, urocortin, on the ingestive behavior of sheep. Intracerebroventricular infusion of these peptides over 4 days decreased the need-free Na intake of Na-repleted sheep. Intracerebroventricular infusion of urocortin, however, did not alter Na intake of Na-depleted sheep. Systemic infusion of ACTH increased, whereas systemic infusion of either urocortin or CRF decreased, Na intake of Na-repleted sheep. The increase in Na intake caused by the peripheral infusion of ACTH was blocked by concurrent i.v. infusion of urocortin, substantiating the inhibitory role of this peptide on Na appetite. Central administration of all peptides and i.v. administration of urocortin or urocortin and ACTH combined decreased food intake. Water intake was not directly influenced by the peptides. Rather, decreased water intake, when observed, was secondary to decreased food intake, as determined by pair-feeding experiments. Whereas systemic infusion of ACTH mimics the increase in Na intake observed in several different stressful situations, CRF and urocortin actually inhibit Na intake, indicating a direct central action overriding any effect of these peptides on ACTH release. Indeed, the inhibition of Na intake by urocortin occurred despite its stimulation of ACTH release and the subsequent increase in peripheral level of cortisol. Thus it would appear that hormones associated with stress have both excitatory and inhibitory influences on Na intake. Presumably, other physiological processes entrained by stress also will be important in determining the quantitative outcome on Na appetite.

Adrenocorticotropic Hormone↗

Fos immunoreactivity in the lamina terminalis of adrenalectomized rats and effects of angiotension II type 1 receptor blockade or deoxycorticosterone.

Neural activity, as measured immunohistochemically by the presence of Fos protein, was determined in the lamina terminalis, a thin strip of tissue forming the anterior wall of the third brain ventricle, after adrenalectomy. Several weeks after surgery, the adrenalectomized rats were maintained with access to water and a low sodium diet for five days. In addition, hypertonic (0.5M) NaCl solution was available for the entire five-day period (sodium available) or only during the first four days (sodium unavailable). The number of neurons expressing Fos, determined at the end of the fifth day, was increased in the adrenalectomized rats with or without NaCl solution to drink. Fos activity in the median preoptic nucleus was increased only in adrenalectomized rats without access to NaCl solution. Treatment of adrenalectomized rats with the sodium-retaining mineralocorticoid hormone, deoxycorticosterone, at the end of the fourth day, decreased Fos expression in the subfornical organ and the organum vasculosum of the lamina terminalis when NaCl solution was available but not when the NaCl solution was unavailable. In the adrenalectomized rats with NaCl solution available, mineralocorticoid treatment decreased both urinary sodium excretion and daily sodium intake. Brain nuclei in the lamina terminalis also became activated in intact rats made sodium deplete by treatment with the diuretic, furosemide. Relative to sodium-deplete intact rats, however, sodium-deplete adrenalectomized rats had a greater number of neurons expressing Fos in the organum vasculosum. Treatment of sodium-deplete rats, adrenalectomized or intact, with the angiotensin II-type 1 receptor antagonist, ZD7155, decreased sodium intake and Fos expression in the subfornical organ but not in the organum vasculosum of the lamina terminalis or median preoptic nucleus. In conclusion, the results demonstrated that activation of the brain nuclei located in the lamina terminalis of adrenalectomized rats was primarily related to sodium deficit and not to the absence of the mineralocorticoid hormones, although the adrenal hormones may have a role in limiting the activation of organum vasculosum of the lamina terminalis during sodium depletion. Furthermore, the results obtained with the administration of the angiotensin receptor antagonist are consistent with the proposal that sodium appetite of the sodium-deplete rat, adrenalectomized or intact, is mediated by circulating angiotensin II acting in the subfornical organ.

Adrenalectomy↗

Differential diagnosis of abuse injuries in infants and young children.

A complete differential diagnosis is essential when assessing potential child abuse injuries. The differential diagnosis provides clinicians with the opportunity to compare injuries that might mimic abuse with actual abuse-related injuries. The differential diagnosis should delineate the injury type, injury site, instruments used, patterns, and the appearance of old or repeated injuries. This article discusses differential diagnoses that should be considered when evaluating injuries in infants and young children.

Age Distribution↗

Collagenase and gelatinase messenger ribonucleic acid expression and activity during follicular development in the rat ovary.

Metalloproteinases are members of a family of proteinases that remodel the extracellular matrix throughout the body. To test the hypothesis that metalloproteinases are regulated by gonadotropin-induced changes during follicular growth, rats were injected with eCG (20 IU, s.c.), and ovaries and serum were collected at the time of eCG administration (0 h) and at 6, 12, 24, 36, or 48 h later for analysis of metalloproteinase mRNA expression, metalloproteinase activity, and steroidogenesis. Serum estradiol levels increased from 18.9 pg/ml at 0 h to 503.8 pg/ml at 48 h. Analysis of mRNA expression was performed for collagenase-3, 72-kDa gelatinase, and 92-kDa gelatinase (n = 3-4). For collagenase-3, eCG stimulated a 32-fold increase in collagenase-3 mRNA at 48 h after eCG injection as compared to that in ovaries collected at the time of eCG administration (i.e., 0-h control). The mRNA levels for 72-kDa gelatinase were 2.8-fold compared to 0 h at 36 h after eCG treatment and returned to control levels by 48 h after gonadotropin treatment. Levels of the 92-kDa mRNA expression peaked at 24 h (4. 2-fold compared to 0 h) and returned to control levels by 36 h. Gel zymography revealed 3 gelatinolytic bands corresponding to the gelatinases of approximately 72 kDa, 92 kDa, and 105 kDa. Analysis of metalloproteinase activity as the degradation of collagen or gelatin per ovary showed an increase in gelatinolytic and collagenolytic activity between 12 and 48 h after eCG treatment. In summary, these findings demonstrate that the gonadotropin induction of folliculogenesis results in changes in the metalloproteinases that may be responsible for extracellular matrix remodeling associated with follicular growth.

Animals↗

Intracerebroventricular infusion of angiotensin II increases water and ethanol intake in rats.

The influence of prolonged ingestion of ethanol on stimulation of water or ethanol intake by intracerebroventricular infusion of ANG II was evaluated in rats. Animals were maintained for 5-6 mo with either 10% ethanol solution or water as their only source of fluid. In both groups of rats, infusion of ANG II caused a large increase in water intake (7-fold) and a lesser increase in 10% ethanol intake (2-fold). The effect of ANG II on the volume of ethanol solution ingested, however, was inversely related to the concentration of the ethanol solution. As the concentration of ethanol solution was decreased, frequency and duration of drinking bouts increased. The intake of sweetened 10% ethanol solution or commercially produced wine during infusion of ANG II was similar to the intake of 10% ethanol and not related to taste preference. In conclusion, chronic consumption of ethanol solution did not appear to adversely effect ANG II stimulation of water intake. The intake of ethanol solution during infusion of ANG II was inhibited by a direct effect of ingested ethanol and/or by indirect effect from metabolized ethanol.

Alcohol Drinking↗

Water drinking in rats resulting from intravenous relaxin and its modification by other dipsogenic factors.

The purpose of the study was to determine whether iv infusion of relaxin would acutely stimulate water drinking in rats and, if it did, whether such drinking is affected by other dipsogenic stimuli or is blocked by centrally administered losartan. iv infusions of human gene 2 relaxin at doses of 25, 40, 55, or 80 microg/kg x h for 1 h induced dose-dependent water drinking in both male and female rats within 15-30 min of commencement of infusions. iv infusion of a nondipsogenic dose of angiotensin II (0.5 microg/h), combined with relaxin (40 microg/kg x h), almost tripled the relaxin-induced water intake. iv infusion of hypertonic (1 M) NaCl did not potentiate relaxin-induced drinking. Intracerebroventricular injection of the angiotensin AT1 antagonist losartan (10 microg) reduced water drinking induced by iv infusion of relaxin. The water drinking induced by iv infusion of relaxin in the rat suggests that blood-borne relaxin may be a dipsogenic hormone. Potentiation of this relaxin-induced drinking by moderate levels of circulating angiotensin II is additional evidence in support of this view. The results also indicate that a central angiotensinergic neural pathway, utilizing AT1 receptors, subserves relaxin-induced drinking.

Angiotensin II↗

Percutaneous lumbar discectomy with a working endoscope and laser assistance.

The authors describe percutaneous disc surgery performed via the unilateral monoportal method with a C-arm image intensifier, a working endoscope, and an yttrium-aluminum-garnet laser in 300 patients at three community hospitals over a 6-year period. Visualizing the area of the annulus to be fenestrated, verifying the status of the nerve root, inspecting the cavity created, and monitoring laser hemostasis and vaporization all contributed to patient safety. Fewer than 2% of the cases required a second surgery. The only postoperative sequelae recorded were one psoas hematoma, which resolved, and sympathetic mediated pain in 5% of the patients who responded to appropriate treatment. For treatment of a prolapsed lumbar disc, a 1-hour endoscopic procedure performed while the patient receives a neuroleptanalgesic continues to be a significant surgical alternative.

Journal Article↗

Molecular characterization of Fiji disease fijivirus genome segment 9.

This is the first report of sequence from Fiji disease fijivirus (FDV), the type member of the genus Fijivirus of the family Reoviridae. FDV genome segment (S9) comprised 1843 nt and contained two non-overlapping ORFs, separated by a 57 nt intergenic region. S9 ORF 1 comprised 1008 nt and encoded a 335-amino-acid polypeptide (predicted molecular mass 38.6 kDa), while ORF 2 comprised 627 nt and encoded a 208-amino-acid polypeptide (predicted molecular mass 23.8 kDa). The 5' and 3' non-coding regions were 49 and 102 nt, respectively. The S9 terminal sequences were 5' AAGUUUUU------UGUC 3', and located immediately adjacent to these sequences were 12 bp imperfect inverted repeats. The entire S9 ORF 1 and the hydrophilic regions of S9 ORF 2 were each expressed as a fusion protein with the maltose-binding protein in Escherichia coli. Antibodies produced against the ORF 1 fusion protein reacted strongly with a protein of approximately 39 kDa present in both crude extracts of FDV-infected sugarcane and partially purified FDV preparations. In contrast, antibodies raised against the modified ORF 2 fusion protein did not react with any proteins in the same samples. Further, polyclonal antibodies produced against partially purified FDV reacted with the ORF 1, but not the modified ORF 2, fusion protein. These results indicate that FDV S9 ORF 1 encodes a major structural protein, while ORF 2 probably encodes a non-structural protein.

Amino Acid Sequence↗

Interaction of circulating hormones with the brain: the roles of the subfornical organ and the organum vasculosum of the lamina terminalis.

1. Most circulating peptide hormones are excluded from much of the brain by the blood-brain barrier. However, they do have access to the circumventricular organs (CVO), which lack the blood-brain barrier. Three of the CVO, the subfornical organ (SFO), organum vasculosum of the lamina terminalis (OVLT) and area postrema, contain neurons responsive to peptides such as angiotensin II (AngII), atrial natriuretic peptide and relaxin. 2. We have studied the patterns of neuronal activation, as shown by Fos expression, in the SFO and OVLT in response to systemically infused AngII, relaxin or hypertonic saline and have found subgroups of neurons activated by the different stimuli. 3. Systemic infusion of relaxin or hypertonic saline activated neurons almost exclusively in the outer regions of the SFO and in the dorsal cap of the OVLT. Many of these neurons send axonal projections to regions of the brain subserving vasopressin secretion and thirst, such as the median preoptic, supraoptic and hypothalamic paraventricular nuclei. 4. At moderate blood concentrations, AngII only stimulates neurons in the inner core of the SFO and lateral regions of the OVLT. Higher levels of AngII in the bloodstream activate additional neurons in the outer parts of the SFO that connect to the supraoptic, paraventricular and median preoptic nuclei and these probably mediate water drinking and vasopressin secretion induced by blood-borne AngII. The efferent connections and the functions mediated by angiotensin-sensitive neurons in the inner core of the SFO and lateral part of the OVLT are unknown.

Angiotensin II↗