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Biomedical subjects

D A Powell

Publications and source records attributed to D A Powell.

At least 91 records · Page 5Linked to original sources
PubMed1987

High resolution proton NMR spectroscopy of human amniotic fluid.

Human amniotic fluid (HAF) is a dynamic system whose characteristics depend on continuous interchanges between fetal and maternal circulations. HAF reflects not only the environment of the fetus but may also provide information about fetal development or pathology. The concentration of HAF constituents varies with gestational age and pathological states. The number of the compounds currently implicated in fetal developmental pathology are relatively few. Currently used assay methods are not adequate to totally explain or predict the complex biochemistry of the fetus. The purpose of this work was to investigate HAF with NMR spectroscopy. In the present study HAF was obtained from 47 women undergoing routine amniocentesis. Cells were separated for karyological analysis and the supernatant was acid-extracted, lyophilized and re-suspended in D20 resulting in a concentration increase over native fluid. 1H NMR spectra were obtained at 360 MHz and 60 MHz. Eighteen compounds including several amino acids, were identified using parallel reference and standard addition protocols. NMR spectroscopy detected compounds of known clinical importance including glucose, leucine, isoleucine, lactate and creatinine. In conclusion, we have demonstrated that a number of physiologically relevant compounds are readily observable in HAF using 1H NMR spectroscopy. This technique can currently provide valuable information regarding HAF composition and has the potential of being used in vivo in the future.

Amniotic Fluid↗
PubMed1987

Comparison of 3H-spiperone binding in caudate nuclei of rabbits and rats.

3H-Spiperone binding and inhibition by competing ligands were studied in caudate nucleus homogenates from Sprague-Dawley rats and New Zealand albino rabbits. 3H-Spiperone binding sites were very similar in the two species and had pharmacological profiles characteristic of D2-dopamine receptors, in accordance with previous reports. However, differences occurred between the species in the potencies with which dopaminergic ergots and other drugs interacted with these binding sites and with regard to the compounds used to define specific binding. These findings suggest that slight differences in relative proportions of subtypes of 3H-spiperone binding sites, or of neuroleptic potencies at these subtypes, may exist between rabbits and rats.

Animals↗
PubMed1987

3H-2-deoxyglucose uptake after electrical stimulation of cardioactive sites in insular cortex and mediodorsal nucleus of the thalamus in rabbits.

The uptake of 3H-2-deoxyglucose (3H-2-DG) in selected brain structures was determined subsequent to electrical stimulation of insular cortex (Ins) and the mediodorsal (MD) nucleus of the thalamus in rabbits. Stimulation of Ins elicited parasympathetic-like responding (i.e., bradycardia and depressor responses); whereas MD stimulation produced sympathetic-like responses (bradycardia and pressor responses). Stimulation of Ins also resulted in increased 3H-2-DG activity in ipsilateral MD and the ventromedial/ventroposterior complex as well as the contralateral Ins compared to nonstimulated control subjects. The central nucleus of the amygdala also showed increased activity after Ins stimulation. In 2 animals stimulation of Ins resulted in increased 3H-2-DG activity in the caudate/putamen complex. Stimulation of MD resulted in ipsilateral increases in 3H-2-DG activity in the midline, agranular prefrontal cortex, as well as the ipsilateral Ins, and the caudate nucleus and putamen/globus pallidus complex. Two animals also showed increases in 3H-2-DG activity in ipsilateral substantia nigra. However, no increased activity was observed in the lateral hypothalamus, the parabrachial nuclei, the nucleus tractus solitarius, or the dorsal motor nucleus of the vagus, although it has been shown that efferents from Ins reach these areas. A more significant finding however, was that the reciprocal connections of MD and Ins appear to be activated by stimulation of either structure, even though their relationship to autonomic function appears to be quite different.

Animals↗
PubMed1987

Epidemiology, diagnosis, and management of Malassezia furfur systemic infection.

Malassezia furfur, a normal skin flora yeast, generally associated with very mild superficial skin infections, has become an opportunistic pathogen in patients with deep-line vascular catheters. The use of intravenous fat emulsions appears to have altered the microenvironment of the catheter and allowed colonization and subsequent infection. Dissemination of the organism appears to be limited to the lungs, which may have been previously altered by vascular lipid deposition. Because of the serious underlying disease(s) of patients with M. furfur catheter sepsis, it is difficult to determine the exact role of the organism in the overall status of the patients. At the very least, however, catheter removal or discontinuance of the fat emulsion therapy may be required. Antifungal therapy without either of these two steps has not been shown to be efficacious. Physicians must maintain a high index of suspicion of M. furfur catheter sepsis in the appropriate clinical setting, and laboratory investigators must be prepared to provide appropriate diagnostic methods.

Adult↗
PubMed1987

Malassezia furfur skin colonization of infants hospitalized in intensive care units.

We studied the prevalence of Malassezia furfur skin colonization of infants hospitalized in our neonatal and infant cardiac and surgical intensive care units by culturing at monthly intervals. Of 361 infants studied over 1 year, 133 (36.8%) had at least one positive culture for M. furfur. Colonized infants, compared with noncolonized infants, had younger mean gestational age (32.4 vs 35.2 weeks, P less than 0.01), lower mean birth weight (1.76 vs 2.31 kg, P less than 0.01), a longer stay in hospital (Wilcoxon P less than 0.01), and more mean days use of an incubator (12.7 vs 7.6 days, P less than 0.01), lamb wool (12.9 vs 8.2 days, P less than 0.01), paper tape (10.8 vs 8.2 days, P less than 0.01), and Op-Site tape (14.1 vs 10.1 days, P less than 0.01). These data suggest that hospitalization in an infant intensive care unit often leads to M. furfur colonization. Although frequent adult handling may be a source, other aspects of intensive care will require careful scrutiny to define more completely the risk factors leading to M. furfur colonization of ill infants.

Birth Weight↗
PubMed1987

Scanning electron microscopy of Malassezia furfur attachment to Broviac catheters.

Malassezia furfur has been increasingly associated with Broviac-catheter-related sepsis in infants receiving fat emulsions for parenteral alimentation. We examined by scanning electron microscopy the appearance of M. furfur attached to Broviac catheter segments mock-infected in vitro and to Broviac catheters removed from two infants with catheter-related sepsis. In vitro attachment occurred equally on external and internal surfaces of the catheters. Although some organisms were attached next to surface defects in the catheters, we could not determine if such defects were preferential sites of attachment. In the patient catheters, a dense coating of yeast cells was found adhering to the luminal surface, most abundantly near the tip. No organisms were seen on the external surface of the catheters. These findings show the need to examine the mechanisms of intraluminal catheter colonization in order to understand better the pathogenesis of M. furfur infections.

Catheterization↗
PubMed1987

In vitro activity of systemic antifungal agents against Malassezia furfur.

The activity of four antifungal agents against 15 systemic (blood and vascular catheter) and 10 superficial (skin) Malassezia furfur isolates was evaluated. MIC ranges were similar for the two groups of organisms: amphotericin B, 0.3 to 2.5 micrograms/ml; flucytosine, greater than 100 micrograms/ml; miconazole, 0.4 to 1.5 micrograms/ml; and ketoconazole, 0.025 to 0.4 micrograms/ml.

Antifungal Agents↗
PubMed1986

Lesions of substantia nigra retard pavlovian somatomotor learning but do not affect autonomic conditioning.

New Zealand albino rabbits with bilateral radio frequency lesions of the substantia nigra (SN) were compared with sham-operated animals on a pavlovian conditioning task in which eyeblink (EB) and heart rate (HR) responses were concomitantly assessed. Lesions of SN increased the number of trials required to reach an EB learning criterion but left the HR conditioned response intact. These results together with other reports in the literature suggest that extrapyramidal motor structures are involved in mediating somatomotor conditioning but are not involved in autonomic learning.

Animals↗
PubMed1986

Ethanol enhancement of Pavlovian conditioning: comparison with instrumental conditioning.

Yoked pairs of rabbits received conditioning and extinction of eyeblink and heart rate responses using aversive Pavlovian versus instrumental avoidance contingencies. A low dose of ethanol (375 mg/kg) increased the amplitude of conditioned eyeblink responses during training and during subsequent extinction following either ethanol or water; this effect was more pronounced in the Pavlovian than the instrumental contingency groups. Ethanol treatment did not affect the cardiac component of the Orienting Reflex to novel tones or heart rate conditioned responses to tone signals, but did bias heart rate responses to tone-shock stimulus pairs in a parasympathetic direction; this effect occurred in both contingency groups but appeared to involve associative factors. These results support the conclusion that mild ethanol intoxication enhances the acquisition of Pavlovian conditioned reflexes, and impairs the ability to modify these responses when stimulus contingencies later change.

Acoustic Stimulation↗
PubMed1986

Pharmacokinetics of netilmicin in premature infants.

The pharmacokinetics of netilmicin were studied in 12 premature infants with proven or presumed sepsis during the first month of life. Eleven of 12 patients received netilmicin 2.5 mg/kg intravenously every 12 h while one 770-gram birth weight infant received 2.5 mg/kg every 18 h. Mean steady-state peak and trough concentrations were 8.9 micrograms/ml and 2.8 micrograms/ml, respectively. Of twelve patients, 11 had trough serum concentration above 2 micrograms/ml and four had trough serum concentrations above 3 micrograms/ml. Mean total body clearance of netilmicin was 0.84 ml/min/kg. The mean clearance of 0.72 ml/min/kg was substantially lower in patients with a mean postnatal age of 2.7 days than the clearance of 1.10 ml/min/kg in patients with a mean postnatal age of 23 days. The mean apparent volume of distribution was 0.63 l/kg; and the mean elimination halflife was 8.6 h. A three-fold interpatient variation in pharmacokinetic parameters was seen. These data suggest the need for careful monitoring of netilmicin serum concentration in premature infants.

Female↗
PubMed1986

Autonomic changes elicited by chemical stimulation of mediodorsal nucleus of the thalamus.

Chronic indwelling cannulas were implanted in the mediodorsal nucleus (MD) of the thalamus in New Zealand albino rabbits. Heart rate (HR), blood pressure (BP), respiration and electromyographic activity (EMG) were recorded subsequent to the injection of saline, l-glutamate, or carbachol through the previously implanted cannulas. Dose related decreases in HR and increases in BP were obtained after administration of both l-glutamate and carbachol at doses in the micromolar range. Control injections through cannulas chronically implanted in the overlying hippocampus or adjacent ventricles resulted in dramatic HR and BP baseline changes in a parasympathetic direction (viz HR and BP decreases) suggesting that the effects obtained with MD placements were due to chemical stimulation of MD. Responses elicited from MD in the present experiment were similar, but not identical, to those produced by electrical stimulation of MD, suggesting that the latter effects were not due to stimulation of fibers of passage.

Animals↗
PubMed1986

Pizotifen (BC-105) attenuates orienting and Pavlovian heart rate conditioning in rabbits.

The cardiac component of the orienting reflex (OR) was elicited in rabbits by 75 dB, 4-sec duration tones of either 304 or 1216 Hz. The conditioned cardiac response was also studied using the same tones and paraorbital electric shock as conditioned and unconditioned stimuli, respectively, using a differential Pavlovian conditioning paradigm. Subcutaneous injections of the central 5-HT antagonist pizotifen (BC-105), the peripheral 5-HT antagonist xylamidine, the central 5-HT agonist d-lysergic acid diethylamide (LSD), and LSD in conjunction with BC-105 were administered 15 min prior to behavioral assessment. Both the heart rate (HR) conditioned response (CR) and the OR consisted of bradycardia. BC-105 attenuated, but xylamidine had no effect on, OR habituation. LSD reduced the magnitude of the OR, an effect which was blocked by BC-105. BC-105 also produced a dose-related attenuation of the bradycardiac HR CR; however, xylamidine had no effect on HR conditioning, suggesting that the attenuation of the HR CR by BC-105 was central rather than peripheral in origin. LSD potentiated the bradycardiac HR CR, but BC-105 in conjunction with LSD attenuated this response. These results suggest that central 5-HT neurons may modulate the magnitude of bradycardiac responses during orienting and aversive Pavlovian conditioning.

Animals↗
PubMed1986

Ethanol enhancement of Pavlovian conditioning.

Rabbits were tested for Pavlovian conditioning and extinction of eye blink and heart rate responses, following water or various doses of ethanol (375-1,500 mg/kg, po). The highest dose suppressed both eye blink and heart rate conditioning during training, whereas the lowest dose enhanced heart rate responses during training and increased eye blink responses during later extinction in a symmetrically state-dependent manner. An intermediate dose (750 mg/kg) administered during training enhanced heart rate responses and suppressed eye blink responses but increased eye blink responses during later extinction following either ethanol or water. Ethanol treatments also suppressed unconditioned responses to shock and increased locomotor activity in rabbits; however, these effects differed qualitatively from those that occurred during Pavlovian training and extinction. These results suggest that very low doses of ethanol can enhance the ability of stimuli to elicit Pavlovian conditioned reflexes and impair the ability to adaptively modify these reflexes when stimulus contingencies later change.

Animals↗
PubMed1986

Tobramycin pharmacokinetics in very low birth weight infants.

Tobramycin is commonly used at a dose of 2.5 mg kg-1 12h-1, but this regimen often results in trough serum concentrations exceeding 2 mg l-1. Because of limited data in infants weighing less than 1,000 g at birth, we studied eight newborn infants (gestational age 24-30 weeks; postnatal age 3 X 4 days; birth weight 0.60-0.97 kg) at a modified dosing regimen of 2.5 mg kg-1 18 h-1 or 3.0 mg kg-1 24 h-1. Tobramycin peak and trough serum concentrations ranged from 6.0-10.8 (7.8 +/- 1.5) mg l-1 and 1.2-2.4 (1.7 +/- 0.4) mg l-1, respectively. Serum concentration exceeded 2 mg l-1 in seven of eight patients at 12 h and two of eight at 18 h; none had a trough serum concentration above 2 mg l-1 at 24 h. Total body clearance ranged from 0.55 to 0.82 (0.69 +/- 0.10) ml min-1 kg-1; apparent volume of distribution ranged from 0.44 to 0.71 (0.59 +/- 0.10) 1 kg-1; and elimination half-life ranged from 7.7 to 12.6 (9.9 +/- 1.5) h. These data indicate that the modified dosage regimen of 2.5 mg kg-1 18 h-1 or 3.0 mg kg-1 24 h-1 appears to be more acceptable than the current regimen in achieving effective and safe peak and trough serum concentration of tobramycin in newborn infants weighing less than 1 kg at birth.

Female↗
PubMed1986

Methods for optimal recovery of Malassezia furfur from blood culture.

Malassezia furfur, a recently described agent of catheter-associated sepsis, requires long-chained fatty acids for in vitro growth. To determine optimum conditions for recovery of the organism from blood culture, we compared a radiometric (BACTEC) with a lysis centrifugation-direct agar plating (Isolator) blood culture method. When blood culture isolates of M. furfur were suspended in phosphate-buffered saline and used as inocula, the BACTEC system detected the organisms radiometrically only when bottles were supplemented with lipid compounds; detection was often delayed (greater than or equal to 72 h) when small inoculum sizes were tested. The Isolator pediatric tube system detected growth of M. furfur within 48 h of plating onto a lipid-supplemented agar medium. Simulated blood culture experiments showed that the addition of whole human blood and Intralipid to the BACTEC 6B bottle was associated with rapid lysis of erythrocytes, accumulation of a chocolate brown sediment in the bottles, and fungicidal activity to the M. furfur isolates. In contrast, suspensions of M. furfur in whole human blood were stable for at least 8 h in Isolator tubes and quantitatively recoverable after plating onto agar. Of the two systems studied, the Isolator tube system provided a more suitable procedure for isolation of M. furfur from blood culture.

Blood↗