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Biomedical subjects

S Stanley

Publications and source records attributed to S Stanley.

At least 37 records · Page 2Linked to original sources

Surfactant content in children with inflammatory lung disease.

OBJECTIVE: To determine surfactant profiles of tracheal secretions in mechanically ventilated children with respiratory failure secondary to bacterial pneumonia, viral pneumonitis, adult respiratory distress syndrome (ARDS), and cardiopulmonary bypass. DESIGN: Prospective, cohort study. SETTING: Tertiary, multidisciplinary, pediatric intensive care unit. PATIENTS: One hundred twenty pediatric patients with respiratory failure requiring mechanical ventilation. INTERVENTIONS: Routine tracheal aspirates were collected from children with bacterial pneumonia, viral pneumonitis, ARDS, postcardiopulmonary bypass, and a postsurgical control group. Samples were obtained on days 1, 2, 3, after every week of intubation and on the day of extubation. MEASUREMENTS AND MAIN RESULTS: The tracheal aspirates were analyzed by high-performance liquid chromatography for lecithin/sphingomyelin rations and by enzyme-linked immunosorbent assay for surfactant proteins A and B. Lung compliance and the oxygenation index were measured on each day of sample collection. On day 1, patients with bacterial pneumonia, viral pneumonitis, and ARDS had decreased lecithin/sphingomyelin ration (p < .001), and those patients with bacterial pneumonia and viral pneumonitis had decreased surfactant protein A/protein concentration (p < .001). The lecithin/sphingomyelin ratios and surfactant protein A/protein concentration were significantly different among the groups (p < .001), with the bacterial pneumonia and viral pneumonitis groups having higher lecithin/sphingomyelin ratios and increased surfactant protein concentrations before extubation. Pulmonary compliance was lower and the oxygenation index was higher than controls (p < .001) in patients with bacterial pneumonia, viral pneumonitis, and ARDS. Pulmonary compliance was correlated weakly with lecithin/sphingomyelin ratio (r2 = .11, p < .001) and surfactant protein A/protein concentration (r2 = .03, p < .05). Surfactant protein B was similar in the diagnostic groups. Surfactant content in tracheal secretions from cardiopulmonary bypass patients was equivalent to controls. CONCLUSION: Abnormal tracheal aspirate surfactant phospholipids and surfactant protein A were noted in children with bacterial pneumonia, viral pneumonitis, and ARDS, but not in children on cardiopulmonary bypass.

Cardiopulmonary Bypass↗

Determination of highest no effect dose (HNED) for local anaesthetic responses to procaine, cocaine, bupivacaine and benzocaine.

The highest no effect doses (HNEDs) for the local anaesthetic (LA) effects of procaine, cocaine, bupivacaine and benzocaine were determined using the heat lamp/hoof withdrawal model of Kamerling et al. (1985b) and the abaxial sesamoid block model of local anaesthesia. The heat lamp rapidly (4 or 5 s) increased the temperature of the superficial skin layers of the pastern to about 90 degrees C, at which point the animal sharply withdrew its hoof. Effective LA blockade precluded this response and superficial skin temperatures exceeded 120 degrees C. Thermal stimulus experiments were routinely terminated after 10 s of exposure to prevent undue tissue damage. Following abaxial sesamoid block with bupivacaine, the HNED for that drug was about 0.25 mg/site. Increasing the dose to 2 mg/site apparently produced complete and prolonged LA blockade. Analogous work showed that the HNED for procaine was about 2.5 mg/site. Similarly, the dose response curve for procaine was parallel with that of bupivacaine but was shifted 10-fold to the right. The duration of the LA response following procaine injection was less than for bupivacaine with the statistically significant response following 40 mg/site injection lasting less than 45 min. Cocaine was less potent than procaine, showing a shallower dose response curve. The HNED for cocaine was less than 5 mg/site, although at this dose the duration of action was extremely short (< 7.5 min). Benzocaine had no significant LA action when a dose of 800 mg was applied topically as a 5% preparation. These results show that the HNEDs for bupivacaine and procaine are remarkably low, that cocaine is somewhat less potent as a LA than might be expected, and that 5% topical benzocaine has no significant pharmacology. The small doses of bupivacaine and procaine producing effective local anaesthesia suggests that developing plasma thresholds for these agents is likely to be very challenging.

Anesthetics, Local↗

Regulatory significance of procaine residues in plasma and urine samples: preliminary communication.

Plasma and urinary concentrations of procaine and the duration of response to procaine after its administration as a local anaesthetic to horses were studied. Following injection of a clinical dose of procaine HCl (80 mg), the concentration of procaine in plasma was less than the lower limit of quantitation and unsuitable for threshold determination. Therefore, the urinary concentration of procaine was determined after injection of a dose of 5 mg procaine HCl, the highest no-effect dose (HNED) of this agent. Free unconjugated procaine in equine urine reached a peak concentration of 23.7 ng/mL, while total (unconjugated plus conjugated) procaine peaked at 37.9 ng/mL (mean urine pH of 8.5). Because a basic drug may concentrate substantially in acidic urine, a threshold concentration of 25 ng/mL of unconjugated procaine is a reasonable and conservative threshold for procaine at this time. Horses were administered abaxial sesamoid blocks containing 2% procaine HCl (40, 80, 160 and 320 mg) and 2% procaine HCl (40 and 320 mg) with epinephrine (1:100,000) in local anaesthetic experiments. There was a significant local anaesthetic (LA) effect for all doses of procaine HCl with the duration of effect ranging from 30 min (40 mg) to 60 min (320 mg). The addition of epinephrine significantly increased the duration of local anaesthesia to 180 min for a 40 mg dose and 420 min for a 320 mg dose. Because epinephrine may extend the duration of local anaesthesia beyond a reasonable period of confinement for horses before the starting time of a race, the increased LA effect following the addition of epinephrine to procaine has regulatory significance.

Anesthetics, Local↗

Character and duration of pharmacological effects of intravenous isoxsuprine.

Isoxsuprine is a therapeutic medication used to treat navicular disease and other lower limb problems in horses and is one of the more frequently detected therapeutic agents in racing horses. In a crossover study, horses were administered isoxsuprine i.v. to determine the character and duration of its pharmacological effects. Isoxsuprine significantly increased heart rate 5-150 min following injection. Unrestrained activity following isoxsuprine treatment was significantly greater than control activity for 105 min after treatment. There was an apparent, although statistically nonsignificant, increased cutaneous blood flow resulting in visible water vapour and sweat production 5-60 min after administration. Initially, there was no difference in skin temperature between control and isoxsuprine treatment values; however, skin temperature decreased below control values 45-120 min after injection. Concurrently, there was a significant decrease in rectal temperature reflecting a decrease in body core temperature. Using infrared thermography, a significant decrease in superficial skin temperature of the front legs occurred 30-240 min after treatment. Isoxsuprine also reduced smooth muscle tone, which was apparent by decreased tone of the internal anal sphincter 10-180 min after treatment. It was concluded that the measurable pharmacological effects of i.v. isoxsuprine are short lived, since none of the above responses were apparent 4 h or more after i.v. administration.

Animals↗

Calcitonin is a physiological inhibitor of prolactin secretion in ovariectomized female rats.

Calcitonin (CT) inhibits secretion of PRL when administered intravenously in rats and humans. It also inhibits PRL release from cultured rat anterior pituitary (AP) cells. Recent evidence suggests that CT-like immunoreactive peptide is synthesized and released from the AP gland. However, its physiological role in the regulation of PRL secretion has not been understood. Present studies tested the role of endogenous pituitary CT (pit-CT) in the regulation of PRL secretion in vivo by passive immunization. In the first group of experiments, ovariectomized (ovx) adult female rats were administered either preimmune or anti-salmon CT (sCT) serum, and their serum PRL levels were analyzed at various time points up to 3 h. A second group of experiments examined the effects of anti-sCT serum and dopamine on PRL release from cultured rate AP cells. In the next group of experiments, the regional distribution of pit-CT secretion was examined in different sections of the AP gland. In the last set, CT-like activity of AP extract was tested in neonatal rat kidney cells, which respond to CT with an increase in cAMP accumulation. These experiments also tested whether anti-sCT serum reduces AP extract-induced increase in cAMP accumulation. The results suggest that anti-sCT serum dramatically increased serum PRL levels (by 5-fold) of ovx rats within 30 min of administration. The serum PRL levels declined gradually after the peak. However, a significant increase in serum PRL levels was maintained by the anti-sCT serum for the duration of the experiment. The anti-serum also induced a significant increase in PRL release from cultured AP cells when added to the presence or absence of dopamine. The distribution profile of pit-CT within the AP gland suggests that the release of pit-CT immunoreactivity was significantly greater in the inner sections, and anti-sCT serum also caused greater increase in PRL release in these sections. Finally, AP extract and sCT stimulated cAMP accumulation in neonatal rat kidney cells, and anti-sCT serum significantly reduced AP extract-induced cAMP accumulation. These results demonstrate that pit-CT is an important regulator of tonic PRL secretion in female rats and can potently inhibit PRL secretion even in the presence of dopamine.

Animals↗

Peptide-specific antibodies as probes of the topography of the voltage-gated channel in the mitochondrial outer membrane of Neurospora crassa.

The voltage-dependent anion-selective channel (VDAC) in mitochondrial outer membranes is formed by a polypeptide (M(r) 31,000) coded by a nuclear gene whose cDNA sequence is known for several organisms. Antibodies have been raised against synthetic peptides corresponding to four different regions in the predicted sequence of the VDAC polypeptide of the fungus Neurospora crassa (residues 1-20, amino terminus; 195-210, 251-268, and 272-283, carboxyl terminus). Specificity of the antibodies has been characterized in terms of binding to peptides or fungal mitochondria on microtiter plates and binding to mitochondrial proteins of several species in Western blots. Reactivity of three of the four antibodies with fungal mitochondria in suspension increases with lysis of outer membranes, indicating that the respective epitopes (including those near the amino and carboxyl termini) are exposed on the surface of the outer membrane that faces inside the mitochondrion. Preincubation of mitochondria with a polyanion that modulates VDAC voltage dependence strongly inhibits binding of the antibody against residues 251-268, whose epitopes are on the outer mitochondrial surface.

Amino Acid Sequence↗

Developing educational programmes for nurses that meet today's addiction challenges.

Since undergraduate curricula have in the past offered little substance abuse content, bold and innovative educational programmes are necessary to prepare nurses for the addiction challenges of the 1990s. The University of Kansas and the American Nurses' Foundation (ANF) recently addressed the problem when they were jointly funded by the John W. and Effie E. Speas Memorial Trust to present an alcohol and other drug education project targeted to nurses practicing in the local community. 60 nurses in key clinical settings were given an opportunity to receive general information about substance abuse through two, 2-day workshops. The purposes of the project were; (1) to plan and develop materials for an alcohol and other drug abuse (AODA) curriculum for practicing nurses in a variety of clinical areas; (2) to assess the effectiveness of the programme through on-site and post-workshop participant evaluations; (3) and to refine the curriculum and materials according to evaluation data. Results indicated that participants' knowledge of AODA was significantly increased by the workshop. Attitudes also changed in two areas, permissiveness and belief in treatment interventions. Decreased permissiveness toward substance abuse persisted 3 months after the workshop indicating this may be a lasting change. The conclusion is that education can lead to a change in knowledge and attitudes toward substance abuse.

Curriculum↗

Evaluation of threshold doses of drug action in the horse using hematocrit values as an indicator.

This study was designed to explore the use of hematocrit values as possible indicators of the threshold doses of adrenergic drugs in the performance horse. Acepromazine, detomidine, and fluphenazine were tested for their effects on hematocrit values, with the threshold dose for these effects investigated. Hematocrit values were shown to be quite sensitive to the administration of acepromazine with doses as low as 50 micrograms/horse producing detectable depressions in hematocrit values for up to 2 hours. Increasing the dose increased the magnitude of the effect, but did not appear to prolong it, while in contrast, reducing the dose to below 25 micrograms/horse totally eliminated the effect. The alpha-2 agonist detomidine produced a similar depression in hematocrit values, although doses of 10 micrograms/kg or approximately 5 mg/horse, were needed to produce a measurable effect. The anti-psychotic fluphenazine, which is believed to be an illegally administered drug in race horses, had no significant effect on hematocrit values when comparable doses were administered. In addition, the results of monitoring the hematocrit values of six horses for 48 hours suggested that the variations seen may be partially related to circadian factors, with peak values occurring in the afternoon hours.

Acepromazine↗

Ureaplasma urealyticum demonstrated by open lung biopsy in newborns with chronic lung disease.

Lung biopsy tissue from eight infants with chronic lung disease was evaluated for the presence of Ureaplasma urealyticum. Specimens from four infants grew the organism. Pleural fluid cultures matched lung tissue but tracheal cultures were negative in two babies with positive lung tissue. There were no distinguishing pathologic findings in the four culture-positive infants which could be used to identify them vs. the culture-negative infants. Three culture-positive infants improved clinically after therapy directed at Ureaplasma even though two remained culture-positive. Ureaplasma grows in lung tissue of infants with chronic lung disease, it does not demonstrate any specific standard pathologic findings and tissue cultures do not match endotracheal cultures.

Biopsy↗

Interleukin 6 induces human immunodeficiency virus expression in infected monocytic cells alone and in synergy with tumor necrosis factor alpha by transcriptional and post-transcriptional mechanisms.

The immunoregulatory cytokine interleukin 6 (IL-6) directly upregulates production of human immunodeficiency virus (HIV) in acutely as well as in chronically infected cells of monocytic lineage. In addition, IL-6 synergizes with tumor necrosis factor alpha (TNF-alpha) in the induction of latent HIV expression. Unlike TNF-alpha, upregulation of viral expression induced by IL-6 alone does not occur at the transcriptional level and it is not associated with accumulation of HIV RNA. However, when IL-6 and TNF-alpha synergistically stimulate HIV production, accumulation of HIV RNA and increased transcription are observed, indicating that IL-6 affects HIV expression at multiple (transcriptional and post-transcriptional) levels.

Blotting, Northern↗

Tumor necrosis factor alpha functions in an autocrine manner in the induction of human immunodeficiency virus expression.

Tumor necrosis factor alpha (TNF-alpha) is an immunoregulatory cytokine capable of inducing viral expression in cells chronically infected with the human immunodeficiency virus (HIV), such as the promonocytic line U1 and the T-lymphocytic line ACH-2. In the present study, we demonstrate an autocrine mechanism of TNF-alpha-mediated HIV induction. Stimulation of U1 and ACH-2 cells with phorbol 12-myristate 13-acetate (PMA) resulted in the induction of TNF-alpha mRNA and the secretion of TNF-alpha. Of note is the fact that anti-TNF-alpha antibodies significantly suppressed the expression of HIV in PMA-stimulated U1 and ACH-2 cells. Furthermore, anti-TNF-alpha antibodies also suppressed both the constitutive and inducible levels of viral expression in the chronically infected promonocytic clone U33.3. This study illustrates the interrelationship between the regulation of HIV expression and normal immunoregulatory mechanisms in that virus expression, both constitutive and induced, can be modulated by an autocrine pathway involving TNF-alpha, a cytokine involved in the complex network of regulation of the normal human immune response.

Antibodies↗