Biomedical subjects

D A Powell

Publications and source records attributed to D A Powell.

At least 37 records · Page 2Linked to original sources

PubMed2000

A general synthetic method for the formation of substituted 5-aminotetrazoles from thioureas: a strategy for diversity amplification.

A general method for the synthesis of 5-aminotetrazoles is outlined using the mercury(II)-promoted attack of azide anion on a thiourea. The reaction proceeds through a guanyl azide intermediate, which undergoes electrocyclization to the tetrazole. The method is high yielding and provides access to mono-, di-, and trisubstituted 5-aminotetrazoles, targets of potential interest for combinatorial library development.

Crystallography, X-Ray↗

PubMed2000

Colitis in a female tamarin (Saguinus mystax).

An adult wild-caught female tamarin (Saguinus mystax) housed in a biomedical research facility was found moribund and extremely dehydrated, with severe diarrhea. She initially responded to supportive therapy but died 3 days later. Necropsy findings included hyperemia of the colonic mucosa, mesenteric lymphadenopathy, acanthocephalid parasites (Prosthenorchis elegans) embedded in the mucosa of the terminal ileum and cecum, and free filarid nematodes (Dipetalonema sp.) in the abdominal cavity. Campylobacter sp. was recovered from the colon. With the exception of changes associated with the parasites, significant histologic changes were limited to the colon. Changes consistent with acute enteric viral infection were found against a background of chronic inflammation. Enterocytes were variably hypertrophied, degenerate, and attenuated. Numerous epithelial syncytial cells were present, and some affected cells (uni- as well as multinucleated) contained intranuclear inclusions. Lymphoid follicles were mildly depleted and contained rare syncytia. Measles (Morbillivirus) infection was confirmed by using immunohistochemistry, reverse transcriptase polymerase chain reaction, and Southern blot analysis. In contrast to the cutaneous rash, respiratory involvement, and low mortality characteristic of Old World monkeys with measles, severe diarrhea with high mortality occurs in New World monkeys with this disease. In addition, our case differs from previous reports of measles in New World monkeys in that syncytial cell formation apparently was limited to the colon of our animal.

Animals↗

PubMed1999

Pavlovian heart rate and jaw movement conditioning in the rabbit: effects of medial prefrontal lesions.

An experiment was conducted in which jaw movements (JM) and heart rate (HR) were concomitantly assessed in rabbits during simple Pavlovian conditioning. A 2-s 1200-Hz tone was the conditioned stimulus (CS) and an intraoral 1-cc pulse of 0.5 M sucrose-water solution was the unconditioned stimulus (US). Sham and medial prefrontal (mPFC)-lesioned animals received paired CS/US training with a 70- to 75-dB CS and were compared with sham- and mPFC-lesioned animals that received explicitly unpaired CS/US presentations. The percentages of JM CRs were significantly greater in the paired than the unpaired groups, but mPFC lesions had no effect on this measure. Conditioned HR decelerations occurred only in the paired groups and then only during the first session of training. Moreover, these CS-evoked cardiac decelerations were somewhat attenuated by the mPFC lesion. CS-evoked HR accelerations, which were significantly greater in unpaired than in paired animals, occurred during the four subsequent sessions. These results suggest that a CS-evoked cardioinhibitory process, mediated by the mPFC, is engendered by Pavlovian appetitive conditioning, as has been previously demonstrated for aversive conditioning. However, during JM conditioning these inhibitory changes are quickly replaced by tachycardia, possibly related to increased nonspecific somatomotor activity, since the tachycardia was somewhat greater in the unpaired animals.

Animals↗

PubMed1999

A behavioral stages model of classical (Pavlovian) conditioning: application to cognitive aging.

In the present article, it is argued that a five-stage sequential model of the behavioral and neurophysiological events that occur when organisms are exposed to signals predicting significant events suggests that classical conditioning produces multiple memory traces involving both excitatory and inhibitory processes. Further, these multiple brain structures and associated neurophysiological mechanisms are beginning to be understood; thus, using Pavlovian conditioning techniques to study aging and cognitive functions may provide insights into which brain structures or mechanisms are responsible for more general age-related declines in associative learning and memory. The evidence for this model is briefly reviewed and studies suggesting age-related effects on classical conditioning of various response systems are described within the context of the brain structures implicated by the model.

Aging↗

PubMed1999

Suspected ciliary block associated with Viscoat use.

Ciliary block or malignant glaucoma is thought to be caused by the misdirection of aqueous into the vitreous. It is refractory to medical treatment and often requires vitreous aspiration. We present a case of ciliary block glaucoma caused by sodium chondroitin sulfate-sodium hyaluronate (Viscoat) gaining access to the vitreous through an unsuspected, small zonular dialysis. Vitrectomy performed through a peripheral iridectomy resolved this severe condition.

Adult↗

PubMed1998

Both medial prefrontal and amygdala central nucleus lesions abolish heart rate classical conditioning, but only prefrontal lesions impair reversal of eyeblink differential conditioning.

Rabbits with lesions of either medial prefrontal cortex (mPFC) or amygdala central nucleus (ACN) were compared with sham-lesioned animals during differential and reversal classical conditioning of the eyeblink (EB) and heart rate (HR) response. Lesions of the mPFC, but not ACN, produced a severe impairment in EB reversal conditioning, but neither lesion affected original discrimination. However, both mPFC and ACN lesions produced a severe attenuation of accompanying HR decelerations during both initial differentiation and reversal. These results suggest that mPFC processing of Pavlovian conditioning contingencies affects not only the autonomic component of learning but preservative somatomotor conditioning as well, whereas ACN processing affects only the autonomic component.

Amygdala↗

PubMed1998

Lesions of the midline thalamic nuclei impair classical conditioning under partial but not continuous reinforcement conditions.

Rabbits with lesions of the midline thalamic nuclei were compared to rabbits with sham lesions on classical eyeblink (EB) and heart rate (HR) conditioning. Separate groups of sham and lesioned animals received either 25, 50 or 100% reinforcement with a periorbital shock unconditioned stimulus. Animals with lesions showed slightly impaired EB conditioning, compared to sham animals, under the partial but not continuous reinforcement schedules. Midline lesions also reduced the magnitude of the decelerative HR conditioned response under partial but not continuous reinforcement conditions. These findings suggest that the midline thalamic nuclei, like the mediodorsal nucleus of the thalamus, process information required for response selection under non-optimal learning conditions.

Animals↗

PubMed1998

Efficacy of itraconazole in children with Trichophyton tonsurans tinea capitis.

BACKGROUND: Tinea capitis is prevalent in children. Although widely used as the drug of choice, the response to griseofulvin may be incomplete and an extended duration of therapy is often required. The response to newer antifungals has not been methodically evaluated in children with Trichophyton tonsurans infection. OBJECTIVE: Our purpose was to determine the efficacy of itraconazole in children with tinea capitis caused by T. tonsurans. METHODS: Pediatric patients with culture proven tinea capitis were enrolled from a hospital-based primary care clinic between January and December of 1996. Patients were treated with itraconazole 100 mg/day and a selenium sulfide-containing shampoo for 4 weeks. Children were evaluated mycologically and clinically every 2 weeks for 2 months. Patients were considered successfully treated if they were culture negative and clinically improved at the end of the study period. Children who remained culture positive or who were clinically not improved at 2 months were classified as treatment failures and retreated. RESULTS: Twenty-five patients completed the study, and 10 (40%) were successfully treated. Fifteen children required re-treatment: 14 remained culture positive at week 8, and one was mycologically negative but clinically worse. CONCLUSION: Itraconazole at a dose of 100 mg/day for 4 weeks may be effective in less than half of children with T. tonsurans tinea capitis.

Antifungal Agents↗

PubMed1997

Vagal activity predicts eyeblink conditioning in human subjects.

A group of old (mean age 73 years) and young (mean age 19.8 years) human subjects received concomitant eyeblink and heart rate classical conditioning, in which a 1000 Hz tone was the conditioning stimulus and a corneal airpuff was the unconditioned stimulus. Fewer old than young subjects showed eyeblink conditioning and age greatly attenuated the magnitude of the brady-cardiac conditioned heart rate response. The heart rate conditioned response was also significantly smaller in the subjects who failed to show eyeblink conditioning regardless of age, suggesting a relationship between parasympathetic cardiac control and somatomotor learning. The power associated with the respiratory peak in the heart rate spectrum, which is vagal in origin, was also smaller in subjects that failed to show eyeblink conditioning, again suggesting a relationship between parasympathetic cardiac activity and motor learning.

Adolescent↗

PubMed1997

Characterization of single-unit activity in the mediodorsal nucleus of the thalamus during expression of differential heart rate conditioning in the rabbit.

Much recent evidence has shown that the thalamic-prefrontal axis is involved in Pavlovian conditioning in rabbits. However, while single cell activity in the prefrontal cortex has been previously studied during classical conditioning in rabbits, that of its thalamic projection nucleus, the mediodorsal (MD) nucleus, has not. Consequently, in the present research we recorded neuronal activity from individual cells in MD during expression of conditioned bradycardia in rabbits that received differential Pavlovian conditioning in which tones served as conditioned stimuli and periorbital shock served as unconditioned stimuli. The pattern of firing in MD was similar to that evoked in the medial prefrontal cortex (mPFC). Of 84 cells sampled, approximately 35% showed CS-evoked activity. Ninety percent of these cells showed increases in activity, while the remainder were biphasic, showing an initial increase followed by a decrease. Also, like the mPFC, some cells showed initial increases, which declined during CS presentation, while others showed gradual increases which reached their maximum at CS offset. Also some cells were responsive to the CS+ and others to the CS-. Thus, MD cells, like mPFC cells, are somewhat heterogenous with regard to responding to conditional stimuli, although, unlike the mPFC, no strictly inhibitory cells were found.

Animals↗

PubMed1997

Amygdala-prefrontal interactions and conditioned bradycardia in the rabbit.

Damage to the amygdala or medial prefrontal cortex (mPFC) produces deficits in learned autonomic adjustments. Whether connections between these 2 structures are necessary for acquiring classically conditioned heart rate (HR) decelerations was studied. Connections between them were interrupted by unilateral lesions of the mPFC and amygdala, but on opposite sides of the brain. One experiment focused on the mPFC and amygdala central nucleus and a second on the mPFC and amygdala basolateral complex. Bilateral lesions of either structure disrupted the HR conditioned response. The response of the 2 crossed lesioned groups also was smaller than that of the sham-operated and unilateral lesioned groups, but significant conditioned stimulus-evoked bradycardia occurred in both, suggesting that although interactions between the amygdala and mPFC may normally occur during associative emotional responding, these connections are not necessary for the acquisition of conditioned bradycardia.

Amygdala↗

PubMed1997

Lesions of the mediodorsal nucleus of the thalamus and classical eyeblink conditioning under less-than-optimal stimulus conditions: role of partial reinforcement and interstimulus interval.

Rabbits received lesions of the mediodorsal nucleus of the thalamus (MD) or sham lesions and were subjected to classical eyeblink (EB) and heart rate (HR) conditioning. Separate groups of sham and lesioned animals received either 50% or 25% reinforcement with a periorbital shock unconditioned stimulus. Other groups received an interstimulus interval of either 1.0 or 1.5 s. Animals with MD lesions acquired the EB conditioned response (CR) more slowly than sham-lesioned animals with either the 1.5-s ISI or with the 25% reinforcement schedule. The lesions had no significant effect on the HR CR, however. Results suggest that information processed by MD is relayed to the prefrontal cortex and is required for somatomotor response selection under nonoptimal learning conditions.

Animals↗

PubMed1997

Response to initial griseofulvin therapy in pediatric patients with tinea capitis.

OBJECTIVE: To estimate the response rate to initial griseofulvin therapy in pediatric patients with tinea capitis and to determine whether clinical or epidemiologic variables differed between patients responding positively and negatively to therapy. METHODS: A review of patients' medical records with a confirmed diagnosis of tinea capitis was performed retrospectively over a 2-year period. Patients were included only if a positive dermatophyte culture was obtained and the initial prescription for griseofulvin was filled at our pharmacy. Responders were children not returning to the clinic or returning without signs or symptoms of infection. Nonresponders were those returning within 8 months with signs and symptoms of disease, requiring additional therapy. RESULTS: During July 1993-June 1995, 479 positive fungal cultures were confirmed in 474 patients, and 857 prescriptions for griseofulvin were filled for 765 patients at our institution. Of 122 evaluable patients meeting both criteria, 60.7% were classified as responders to initial prescribed therapy. The remaining 39.3% returned to the clinic within 8 months of initial therapy, requiring additional treatment. An additional 10.7% had a recurrence at a later date. There was no correlation between clinical response and dosage, age, race, or gender, although there was a trend toward longer treatment duration among responders. CONCLUSIONS: It is evident that tinea capitis persists in the urban pediatric population. Our data suggest that griseofulvin, the current drug of choice, may be ineffective in at least one-third of pediatric patients with tinea capitis.

Age Factors↗

PubMed1996

Neuronal activity in the medial prefrontal cortex during Pavlovian eyeblink and nictitating membrane conditioning.

The present study assessed Pavlovian eyeblink (EB) conditioning, using tones and periorbital shock as the conditioned and unconditioned stimuli (CS and US), and nictitating membrane (NM) conditioning, using tones and airpuffs as the CS and US. During each experiment, CS-evoked changes in multiple-unit activity (MUA) in the medial prefrontal cortex (mPFC) were recorded. Concomitant heart rate (HR) conditioned responses (CRs) were also recorded. A nonassociative control group received explicitly unpaired presentations of the CS and US in each experiment. Increases in both NM and EB CRs occurred over sessions in the paired, but not the unpaired, groups. Decelerative HR CRs also occurred in the eyeshock, but not the airpuff, group. Although tone-evoked increases in neuronal activity were obtained during 10 initial tone-alone presentations in all groups, this activity habituated over trials. CS-evoked increases in neuronal activity also occurred, but this activity was considerably greater in the group that received periorbital shock as the US. During subsequent extinction trials, decreases in tone-evoked neuronal activity occurred in this group, compared with the previous CS/US paired trials. CS-evoked MUA increases were minimal during all except the pretraining phase of the study in the CS/US unpaired control groups and in the paired airpuff group. These findings show that neuronal activity during associative learning occurs in the mPFC during Pavlovian EB, as well as HR conditioning, but this activity apparently reflects an affective component to learning that is only indirectly related to skeletal conditioning.

Acoustic Stimulation↗

PubMed1996

Subicular lesions disrupt but do not abolish classically conditioned bradycardia in rabbits.

Rabbits and rats received horseradish peroxidase injections in the medial prefrontal cortex, and retrograde labeling was examined in the hippocampus (HC) and subicular complex (SC). Labeled cells were observed in HC and SC in the rat, but only in the SC of the rabbit. In a second experiment, separate groups of rabbits with sham, SC, or cortical control lesions were subjected to differential classical heart rate conditioning, in which 4-s, 75-db tones served as conditioned stimuli and a 3-mA paraorbital shock was the unconditioned stimulus. Although conditioned bradycardia was obtained in animals with SC lesions, it was slower to develop and was much shorter in duration than in the cortical and sham control groups. In the animals with SC lesions, the bradycardiac response was quickly replaced with tachycardia, suggesting a sympathetic bias in these animals.

Animals↗

PubMed1996

Application of the polymerase chain reaction to the diagnosis and management of neonatal herpes simplex virus disease. National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group.

Cerebrospinal fluid (CSF) specimens from 77 neonates with herpes simplex virus (HSV) disease were evaluated retrospectively by polymerase chain reaction (PCR). Samples were collected from 202 infants enrolled in a National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group trial that compared vidarabine with acyclovir for the treatment of neonatal HSV infection. HSV DNA was detected in the CSF of 26 (76%) of 34 infants with CNS disease, in 13 (93%) of 14 infants with disseminated infection, and in 7 (24%) of 29 with skin, eye, or mouth (SEM) involvement. One of the 7 PCR-positive SEM patients subsequently developed severe neurologic impairment. Eighteen (95%) of 19 infants with positive CSF PCR results after the completion of 10 days of antiviral therapy experienced significant morbidity or mortality. Application of PCR to neonatal HSV disease may provide additional information on which clinical decisions may be based, although its diagnostic utility outside the research setting is unproven.

Brain↗

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↗