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Biomedical subjects

D A Powell

Publications and source records attributed to D A Powell.

At least 19 recordsLinked to original sources
PubMed1995

Topical ciprofloxacin for otorrhea after tympanostomy tube placement.

OBJECTIVE: To evaluate the efficacy, systemic absorption, and safety of ototopically administered ciprofloxacin in children with otorrhea associated with tympanostomy tube placement. DESIGN: Nonrandomized, open-label pilot trial with pharmacokinetic determination of the systemic absorption of ototopical ciprofloxacin. SETTING: A pediatric otolaryngology clinic affiliated with Columbus (Ohio) Children's Hospital. PATIENTS: Patients aged 3 to 8 years were enrolled if they had persistent otorrhea associated with tympanostomy tube placement. Other inclusion criteria were culture of Pseudomonas aeruginosa from the drainage material; failure of previous oral antibiotic therapy; and ability to participate in bone conduction audiometry. INTERVENTION: Participants received 3 drops (approximately 60 microL) of 0.3% ototopical ciprofloxacin hydrochloride (Ciloxan, Alcon Laboratories Inc, Forth Worth, Tex), three times a day, for 14 days. Bone conduction audiometry was performed at baseline and on day 14. Patients were examined on days 7 and 14 for efficacy of treatment (improvement, cure, failure) and adverse effects. On day 7, blood samples were drawn just before and 1 hour after the dose was given. Concentrations of ciprofloxacin were measured by high-performance liquid chromatography, with a 5 ng/mL limit of detection. Telephone follow-up was performed on day 44. Parents were asked about adverse effects at days 7, 14, and 44. RESULTS: Mean duration of ear drainage at baseline was 10.7 months (0.75 to 36 months). Ten of 11 infected ears (nine of 10 patients) were improved or cured at day 7. Ten of 11 ears were completely cured at days 14 and 44. No adverse effects were noted or reported by the children's parents. One child had abnormal bone conduction audiometry results at baseline. The results of bone conduction audiometry on day 14 were normal in all children. Trough concentrations of ciprofloxacin were determined in eight of 10 children; and peak concentrations were determined in seven of 10 children. Ciprofloxacin was not detected in the plasma of any child. CONCLUSION: Topical ciprofloxacin was found to be safe and effective in treating otorrhea in children who did not respond to other treatments.

Administration, Topical↗
PubMed1994

Sulfate detection in glycoprotein-derived oligosaccharides by artificial neural network analysis of Fourier-transform infrared spectra.

We report the use of an artificial neural network to analyze the fingerprint region of Fourier-transform infrared (ir) spectra of oligosaccharides for the presence of sulfate groups. This assay can rapidly and nondestructively detect the presence of sulfate in as little as 1 nmol (approximately 2 micrograms) of a glycoprotein-derived monosulfated decasaccharide. The neural network was trained to recognize the presence of sulfate groups by presenting it with 45 ir spectra of sulfated and nonsulfated mono- and oligosaccharides. No prior knowledge of the characteristic ir spectral features of a sulfate group was needed as input. The training process required between 3 and 10 h, while analysis of a spectrum with the trained neural network requires only 0.1 s.

Carbohydrate Sequence↗
PubMed1994

Efferent connections of the medial prefrontal cortex in the rabbit.

The different cytoarchitectonic regions of the medial prefrontal cortex (mPFC) have recently been shown to play divergent roles in associative learning in rabbits. To determine if these subareas of the mPFC, including areas 24 (anterior cingulate cortex), 25 (infralimbic cortex), and 32 (prelimbic cortex) have differential efferent connections with other cortical and subcortical areas in the rabbit, anterograde and retrograde tracing experiments were performed using the Phaseolus vulgaris leukoagglutinin (PHA-L), and horseradish peroxidase (HRP) techniques. All three areas showed local dorsal-ventral projections into each of the other areas, and a contralateral projection to the homologous area on the other side of the brain. All three also revealed a trajectory through the striatum, resulting in heavy innervation of the caudate nucleus, the claustrum, and a lighter projection to the agranular insular cortex. The thalamic projections of areas 24 and 32 were similar, but not identical, with projections to the mediodorsal nucleus (MD) and all of the midline nuclei. However, the primary thalamic projections from area 25 were to the intralaminar and midline nuclei. All three areas also projected to the ventromedial and to a lesser extent to the ventral posterior thalamic nuclei. Projections were also observed in the lateral hypothalamus, in an area just lateral to the descending limb of the fornix. Amygdala projections from areas 32 and 24 were primarily to the lateral, basolateral and basomedial nuclei, but area 25 also projected to the central nucleus. All three areas also showed projections to the midbrain periaqueductal central gray, median raphe nucleus, ventral tegmental area, substantia nigra, locus coeruleus and pontine nuclei. However, only areas 24 and the more dorsal portions of area 32 projected to the superior colliculus. Area 25 and the ventral portions of area 32 also showed a bilateral projection to the parabrachial nuclei and dorsal and ventral medulla. The dorsal portions of area 32, and all of area 24 were, however, devoid of these projections. It is suggested that these differential projections are responsible for the diverse roles that the cytoarchitectonic subfields of the mPFC have been demonstrated to play in associative learning.

Animals↗
PubMed1994

Involvement of subdivisions of the medial prefrontal cortex in learned cardiac adjustments in rabbits.

Electrical stimulation of area 24 and area 32 of the medial prefrontal cortex (mPFC) in rabbits elicited increases in respiration rate and decreases in heart rate (HR) and blood pressure. However, stimulation in area 25 elicited pressor responses and a biphasic HR response consisting of an initial HR increase followed by an HR decrease. Administration of an alpha-adrenergic receptor antagonist eliminated the pressor response and bradycardiac response produced by area 25 stimulation but it had no effect on the bradycardia elicited by stimulation of area 24 or area 32. Lesions centered on area 32 of the mPFC greatly attenuated the conditioned bradycardiac response elicited by paired tone and paraorbital shock presentations. Lesions of area 24 produced a decrease in discrimination between a reinforced conditioned stimulus and a nonreinforced conditioned stimulus but had no effect on the magnitude of the conditioned response. Area 25 lesions had no effect on any aspect of conditioned responding.

Animals↗
PubMed1994

Bloodstream infections in neonatal intensive care unit patients: results of a multicenter study.

For identification of risk factors for bloodstream infection (BSI) among neonatal intensive care unit patients, prospective 6-month studies in three neonatal intensive care units were conducted. BSI was diagnosed in 42 of 376 (11.2%) enrolled infants. Pathogens included coagulase-negative staphylococci, Candida sp., Group B streptococci and Gram-negative species. Patients with BSIs were more likely to die during their neonatal intensive care unit stay than were patients who did not acquire BSIs (6 of 42 vs. 11 of 334, P = 0.007). BSI rate was highest in infants with birth weight < 1500 g (relative risk (RR) = 6.8, P < 0.001), those treated with H-2 blockers (RR = 4.2, P < 0.001) or theophylline (RR = 2.8, P < 0.001) and those with admission diagnoses referable to the respiratory tract (RR = 3.7, P < 0.001). Infants who developed BSI were more severely ill on admission than other infants (median physiologic stability index 13 vs. 10 (P < 0.001) and were of lower gestational age (28 vs. 35 weeks, P < 0.001). In logistic regression analysis, risk of BSI was independently associated only with very low birth weight, respiratory admission diagnoses and receipt of H-2 blockers. Risk of isolation of a pathogen from blood culture was independently associated with Broviac, umbilical vein or peripheral venous catheterization > 10, 7 or 3 days, respectively, at one insertion site. Rate of isolation of a pathogen was higher (9 of 59 (15%)) within 48 hours of a measurable serum interleukin 6 concentration than an interleukin 6 level of 0 pg/ml (10 of 159 (6%), P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗
PubMed1993

Concomitant eyeblink and heart rate classical conditioning in young, middle-aged, and elderly human subjects.

Pavlovian heart rate (HR) and eyeblink (EB) conditioning were assessed in 4 groups of Ss who differed in age: young = 19-33 years, young middle-aged = 35-48 years, old middle-aged = 50-63 years, and old = 66-78 years. A 100-ms corneal airpuff was the unconditioned stimulus and a 600-ms tone was the conditioned stimulus. A nonassociative control group received explicitly unpaired tone and airpuff presentations. All Ss were studied for 2 100-trial sessions separated by approximately 7 days. An impairment in acquisition of both the EB and HR responses occurred in the old and middle-age Ss, but all age groups showed significantly greater conditioning than did the control group. Slight increases in performance resulted from a 2nd session of training. These findings suggest an age-related impairment in a general associative process.

Adult↗
PubMed1992

Reduced PAL gene suppression in Verticillium-infected resistant tomatoes.

In tomato, resistance to the wilt fungus Verticillium albo-atrum is determined primarily by the Ve locus. When two tomato near-isolines which differ at this locus and in their susceptibility to the pathogen were compared, more rapid suberin coating in the xylem of resistant plants correlated closely with a more rapid increase in the activity of phenylalanine ammonia-lyase (PAL; EC 4.3.1.5), an enzyme which is essential to the suberization process. In contrast, levels of mRNA did not increase proportionally to the measured enzyme activities; rather, there was a substantial suppression of mRNA levels in the susceptible tomato line, consistent with a much lower elevation of PAL activity and significantly less vascular coating. The suppression was absent or substantially reduced in the resistant line. The results indicate that the pathogen can suppress defense genes in susceptible plants but suggest that their expression is altered in resistant hosts and that post-transcriptional regulation plays a significant role.

Amino Acid Sequence↗
PubMed1992

Nucleus basalis lesions attenuate acquisition, but not retention, of Pavlovian heart rate conditioning and have no effect on eyeblink conditioning.

Rabbits with lesions of the anterior nucleus basalis of Meynert (nBM) were compared with animals with sham lesions or unoperated control animals on a classical conditioning task in which heart rate (HR) and eyeblink (EB) conditioned responses (CRs) were assessed. The nBM lesions impaired the magnitude of the decelerative HR CR, but had no effect on the EB CR. A second experiment, in which animals were lesioned after acquisition was complete, showed that anterior nBM lesions had no effect on retention of either the HR or EB CR. These data suggest that the anterior nBM may participate in the early stages of information processing in which stimuli are evaluated for their significance based on their association with a reinforcer. However, the anterior nBM is apparently not involved in the selection of a somatomotor response to deal effectively with such changing stimulus contingencies.

Animals↗
PubMed1992

A comparison of multiple-unit activity in the medial prefrontal and agranular insular cortices during Pavlovian heart rate conditioning in rabbits.

Multiple-unit activity (MUA) was recorded from chronically implanted electrodes in the medial prefrontal cortex (PFCm) and the agranular insular cortex (Iag) in separate groups of rabbits during habituation training, followed by aversive Pavlovian conditioning and subsequent extinction training. Control animals received explicitly unpaired presentations of the tone conditioned stimulus (CS) and eye-shock unconditioned stimulus (US). Both the cardiac orientating reflex and the conditioned heart rate response (HR CR) consisted of bradycardia, whereas tone-evoked tachycardia was observed in animals that received unpaired stimuli. Short-latency (less than 20-60 ms), tone-evoked increases in PFCm MUA were observed during the initial trials of habituation training, with their magnitude declining predictably across repeated tone-alone presentations. Subsequent CS/US pairings, however, served systematically to reinstate and enhance this CS-evoked MUA, while both non-associative (unpaired CS/US) and extinction (CS alone) training resulted in significant attenuation of such activity. Unconditioned tone-evoked increases in MUA were also observed in the Iag during habituation; however, such unit responses appeared to be more variable than their PFCm counterparts and were of considerably lesser magnitude. Moreover, in striking contrast to the above PFCm findings, conditioning and non-associative training did not differentially affect overall mean evoked MUA in the Iag, although different post-tone patterns of activity were obtained with the two procedures. The contrasting training effects observed in animals with PFCm vs. Iag electrode placements did not appear to be attributable to differences in regional sensitivity to the US, since excitatory patterns of MUA were elicited by unsignalled presentations of eye-shock at most placements within each cortical field. Accordingly, the present findings are consistent with our previous lesion data in suggesting that, although training-induced changes in PFCm neuronal activity may contribute to the initial events in aversive Pavlovian conditioning, an involvement of the Iag in such processes, if any, remains to be demonstrated.

Acoustic Stimulation↗
PubMed1992

Concomitant heart rate and eyeblink Pavlovian conditioning in human subjects as a function of interstimulus interval.

Pavlovian heart rate and eyeblink conditioning were simultaneously assessed in human subjects. Tone durations of 0.6, 1.1, and 2.1 s were employed in separate groups of subjects as the conditioned stimulus. A 100-ms corneal airpuff, which served as the unconditioned stimulus, overlapped the last 100 ms of the tone in each group, thus producing interstimulus intervals of 0.5, 1.0, and 2.0 s. Other groups of pseudoconditioning subjects received explicitly unpaired tone and airpuff presentations of identical durations but in a pseudorandom sequence so that they never occurred together. The best eyeblink conditioning was observed in the group with the .5-s interstimulus interval, although the 1.0-s group also demonstrated some evidence of eyeblink conditioning. The group with the 2.0-s interstimulus interval showed a lower overall rate of conditioned response occurrence and the highest rate of pseudoconditioned responding. The conditioned heart rate response in all three conditioning groups consisted of cardiac decelerations, but tone-evoked cardiac accelerations were observed in the pseudoconditioning groups. The magnitude of the cardiac deceleration was comparable in all three conditioning groups.

Adult↗
PubMed1992

Human infections due to Malassezia spp.

The genus Malassezia contains three member species: Malassezia furfur and Malassezia sympodialis, both obligatory lipophilic, skin flora yeasts of humans, and Malassezia pachydermatis, a nonobligatory lipophilic, skin flora yeast of other warm-blooded animals. Several characteristics suggest the basidiomycetous nature of these yeasts, although a perfect stage has not been identified. Classically, these organisms are associated with superficial infections of the skin and associated structures, including pityriasis versicolor and folliculitis. Recently, however, they have been reported as agents of more invasive human diseases including deep-line catheter-associated sepsis. The latter infection occurs in patients, primarily infants, receiving parenteral nutrition (including lipid emulsions) through the catheter. The lipids presumably provide growth factors required for replication of the organisms. It is unclear how deep-line catheters become colonized with Malassezia spp. Skin colonization with M. furfur is common in infants hospitalized in neonatal intensive care units, whereas colonization of newborns hospitalized in well-baby nurseries and of older infants is rarely observed. Catheter colonization, which may occur without overt clinical symptoms, probably occurs secondary to skin colonization, with the organism gaining access either via the catheter insertion site on the skin or through the external catheter hub (connecting port). There is little information on the colonization of hospitalized patients by M. sympodialis or M. pachydermatis. Diagnosis of superficial infections is best made by microscopic examination of skin scrapings following KOH, calcofluor white, or histologic staining. Treatment of these infections involves the use of topical or oral antifungal agents, and it may be prolonged. Diagnosis of Malassezia catheter-associated sepsis requires detection of the organism in whole blood smears or in buffy coat smears of blood drawn through the infected catheter or isolation of the organism from catheter or peripheral blood or the catheter tip. Culture of M. furfur from blood is best achieved with Isolator tubes and plating onto a solid medium supplemented with a lipid source. Appropriate treatment of patients requires removal of the infected catheter with or without temporary stoppage of lipid emulsions; administration of antifungal therapeutic agents does not appear to be necessary. Because many patients who develop Malassezia catheter-associated sepsis have severe underlying illnesses, caution must be exercised in attributing all clinical deterioration to Malassezia infection. Our better understanding of how these organisms cause disease awaits the development of a useful typing scheme for epidemiologic studies and further studies on microbial virulence factors and the role of the immune response in pathogenesis.

Dermatomycoses↗
PubMed1992

Efficacy of ibuprofen in pediatric patients with fever.

We studied the efficacy of ibuprofen in 56 infants and children (age 0.5-12 years) with rectal temperature greater than or equal to 38.3 degrees C, using a double-blind randomized placebo-controlled design. Ibuprofen liquid was given as a single dose, 5 mg/kg to 18 patients (group I) and 10 mg/kg to 18 patients (group II); placebo was administered to 20 patients (group III). Temperature and vital signs were measured every 0.5-1.0 hours for 8 hours. Multiple blood samples were also collected over this period; ibuprofen plasma concentrations were measured by HPLC. The mean temperature was 38.3 degrees C in group I, 38.1 degrees C in group II, and 38.9 degrees C in group III during 8 hours after drug or placebo administration. The temperature was significantly lower in group I vs III (ibuprofen 5 mg/kg vs placebo) (p less than 0.0005), and group II vs III (ibuprofen 10 mg/kg vs placebo) (p less than 0.0001). The temperature was also markedly different for patients in group I vs II (ibuprofen 5 mg/kg vs ibuprofen 10 mg/kg) between 4 and 8 hours after the dose (p less than 0.01). The duration of action was longer for ibuprofen 10 mg/kg than 5 mg/kg. The mean maximum decrease from baseline temperature was 1.3 degrees C, 1.8 degrees C and 0.8 degrees C for group I, II and III, respectively. The maximum reduction in temperature occurred at 3-4 hours in the ibuprofen groups, and at 7 hours in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Temperature↗
PubMed1991

Single-unit activity in the dorsomedial prefrontal cortex during the expression of discriminative bradycardia in rabbits.

Much recent evidence suggests that the medial prefrontal cortex (PFCm) participates in the development and/or expression of learned, primary bradycardiac adjustments in rabbits. Accordingly, the present experiments were undertaken to determine whether single-unit activity in the precentral agranular and anterior cingulate regions of the PFCm is systematically affected by differential aversive Pavlovian conditioning and, if so, whether such activity is correlated with concomitant heart rate (HR) variables. In these studies, extracellular recordings were made during a training procedure that involved two distinctive, tone conditioned stimuli (CSs); one of these (CS+) was often paired with eye-shock (unconditioned stimulus, US), whereas the other (CS-) was never so paired. Of the 100 spontaneously-active cells whose activity was so evaluated, 74 were found to be tone-responsive and could be classified as belonging to one of 5 subpopulations on the basis of their specific patterns of evoked changes in discharge; additional data suggested that these cells were also generally responsive to the eye-shock US. Regarding the effects of training, the vast majority of cells in these subpopulations showed greater evoked activity changes on CS+, as opposed to CS-, trials, irrespective of the sign (i.e. increase and/or decrease) of their responses. This finding was not confounded by differences in baseline activity preceding CS+ vs CS- trials, which was generally characterized as being both irregular and unrelated to concomitant HR variables; nor could it be attributed to unconditioned responses biases. Thus, the discriminative activity patterns of these cells appeared to reflect the differential Pavlovian contingencies in effect. Moreover, approximately half of these cells exhibited tone-evoked activity changes that were reliably correlated with concomitant HR changes on a trial-by-trial basis. Consequently, the present data indicate that training-induced changes in the CS-evoked activity of PFCm cells are significantly related to aversively conditioned bradycardia in rabbits.

Animals↗
PubMed1991

Pancreatectomy, amino acids and glucagon: effect on canine renal autoregulation.

Using pancreactectomized (PX) dogs, we recently suggested the importance of glucagon in modulating amino acid-induced increases in renal blood flow (RBF) and glomerular filtration rate (GFR). We have now ascertained whether glucagon's modulatory effect is associated with an impairment in renal autoregulation. As renal arterial pressure (RAP) was reduced to 70 mmHg (the lower limit of the autoregulatory range) in both sham-operated control (C) and PX control dogs, RBF and GFR remained at values that were greater than 90% of their respective controls. In control dogs infused with amino acids (0.051 mmol/kg per min, i.v.), RBF and GFR rose by 26 and 27%, respectively, at baseline RAP. As RAP was reduced to 70 mmHg, RBF and GFR fell by 25 and 37%, respectively. In PX dogs infused with either amino acids or glucagon (0.86 pmol/kg per min, i.v.) alone, RBF and GFR did not increase appreciably at baseline RAP. As RAP was reduced to 70 mmHg in these dogs, RBF and GFR remained at values that were greater than 90% of their respective controls. Yet, in PX dogs infused simultaneously with amino acids and glucagon, RBF and GFR rose by 22 and 24%, respectively, at baseline RAP. Moreover, as RAP was reduced to 70 mmHg, RBF and GFR fell by 22 and 31%, respectively. These data suggest that the ability of glucagon to modulate the renal hemodynamic response to amino acid infusion involves an impairment in renal autoregulation.

Amino Acids↗
PubMed1991

Pharmacokinetics of ibuprofen in febrile children.

Ibuprofen may be an alternative to acetaminophen to control fever in children but little is known about its pharmacokinetics in pediatric patients. We studied 17 patients (age 3-10 yr) with fever; the most prevalent diagnoses were streptococcal pharyngitis and otitis media. Ibuprofen liquid was given as a single dose, 5 mg/kg (9 patients) or 10 mg/kg (8 patients). Multiple blood samples were collected over 8 hours and analyzed by HPLC. The maximum observed serum concentrations of ibuprofen ranged from 17-42 micrograms.ml-1 at 5 mg.kg-1 and 25-53 micrograms.ml-1 at 10 mg.kg-1 doses. Pharmacokinetics did not appear to be affected by ibuprofen dose. Mean tmax, oral clearance and elimination half life were 1.1 h, 1.2 ml.min-1.kg-1, and 1.6 h, respectively in patients at 5 mg.kg-1 doses; the corresponding values were 1.2 h, 1.4 ml.min-1.kg-1, and 1.6 h in those receiving 10 mg.kg-1 doses. There was no relationship between age and ibuprofen kinetics. No adverse effects occurred in any patients. These data suggest that ibuprofen pharmacokinetics may not be affected by dose between 5 and 10 mg/kg or age between 3 and 10 years.

Administration, Oral↗
PubMed1991

Opioid modulation of pavlovian learning in rabbits: involvement of sublenticular pathways.

Intravenous naloxone enhanced, and D-Ala2-Met-enkephalinamide (DALA) impaired, Pavlovian conditioned heart rate discrimination in rabbits (Oryctolagus cuniculus) during initial training trials, compared with saline; naloxone also delayed subsequent extinction of the discrimination. These effects of the opioid treatments on discrimination were abolished by parasagittal knife-cut lesions in the sublenticular substantia innominata that did not, themselves, impair discrimination. Both naloxone and DALA decreased the magnitude and altered the topography of bradycardiac conditioned responses, and the lesions also abolished these effects of the opioid treatments, but they did not alter the effect of naloxone to decrease bradycardiac orienting response magnitude. These findings suggest that fibers in the sublenticular area mediate specifically the effects of systemic opioids on associative functions during Pavlovian cardiac conditioning and extinction.

Animals↗
PubMed1991

Pharmacokinetics of cefuroxime axetil suspension in infants and children.

The pharmacokinetics of cefuroxime axetil suspension in 28 infants and children, ranging in age from 3 months to 12 years (mean, 23 months), were studied. Mean maximum serum cefuroxime concentrations of 3.3, 5.1, and 7.0 micrograms/ml were achieved 3.6, 2.7, and 3.1 h after the administration of doses of 10, 15, and 20 mg, respectively, of cefuroxime axetil suspension per kg of body weight together with milk or milk formula. These concentrations exceed the MICs for common respiratory tract pathogens, including beta-lactamase-producing strains of Haemophilus influenzae and Moraxella (Branhamella) catarrhalis. Following a 10- or 15-mg/kg dose, serum cefuroxime concentrations are similar to those achieved in adults following the administration of a 250-mg cefuroxime axetil tablet. There were linear relationships between dose and both maximum serum cefuroxime concentration and area under the serum drug concentration-verus-time curve. The mean half-life of cefuroxime in serum was independent of dose and ranged from 1.4 to 1.9 h. No cefuroxime axetil (intact ester) was detected in the blood. The intact ester in the urine of four children was measured; however, the amount recovered represented less than 0.1% of the administered dose.

Adolescent↗