PubMed Health⌕ Search

Biomedical subjects

S A Davis

Publications and source records attributed to S A Davis.

At least 19 recordsLinked to original sources
PubMed2006

Effects of (+/-)3,4-methylenedioxymethamphetamine, (+/-)3,4-methylenedioxyamphetamine and methamphetamine on temperature and activity in rhesus macaques.

Severe and malignant hyperthermia is a frequently reported factor in emergency department (ED) visits and fatalities in which use of amphetamine drugs, such as (+/-)3,4-methylenedioxymethamphetamine (MDMA), (+/-)3,4-methylenedioxyamphetamine (MDA) and (+)methamphetamine (METH), is confirmed. Individuals who use "ecstasy" are also often exposed, intentionally or otherwise, to several of these structurally-related compounds alone or in combination. In animal studies the degree of (subcritical) hyperthermia is often related to the severity of amphetamine-induced neurotoxicity, suggesting health risks to the human user even when emergency medical services are not invoked. A clear distinction of thermoregulatory risks posed by different amphetamines is therefore critical to understand factors that may produce medical emergency related to hyperthermia. The objective of this study was therefore to determine the relative thermoregulatory disruption produced by recreational doses of MDMA, MDA and METH in nonhuman primates. Body temperature and spontaneous home cage activity were monitored continuously in six male rhesus monkeys via radiotelemetric devices. The subjects were challenged intramuscularly with 0.56-2.4 mg/kg MDMA, 0.56-2.4 mg/kg MDA and 0.1-1.0 mg/kg METH. All three amphetamines significantly elevated temperature; however the time course of effects differed. The acute effect of METH lasted hours longer than MDA or MDMA and a disruption of nighttime circadian cooling was observed as long as 18 h after 1.0 mg/kg METH and 1.78-2.4 mg/kg MDA, but not after MDMA. Activity levels were only reliably increased by 0.32 mg/kg METH. It is concluded that while all three substituted amphetamines produce hyperthermia in rhesus monkeys, the effects do not depend on elevated locomotor activity and exhibit differences between compounds. The results highlight physiological risks posed both by recreational use of the amphetamines and by current trials for clinical MDMA use.

3,4-Methylenedioxyamphetamine↗
PubMed2002

Dependence of population response to fertility control on the survival of sterile animals and their role in regulation.

The species for which fertility control is presently used, or for which it is being developed, range from small mammal pests, such as the house mouse (Mus domesticus), to large mammals, such as the African elephant (Loxodonta africana). However, the possibility of a population response other than a reduction in abundance proportional to the fraction of animals rendered infertile has been shown in field trials. For example, when intermediate levels of sterility were imposed on wild populations of European rabbits (Oryctolagus cuniculus), there was an increase in their abundance, on an annual basis, due to enhanced survival of juveniles and adult females. In this article, we relate intraspecific regulatory processes to the response of populations to fertility control using a set of density-dependent structured-population models. In each of the models, the population is exposed periodically to a fertility control agent that renders a fraction of fertile females sterile. Although our intention is not to predict the population response of any one particular species, the results of the models are illustrated using parameter values that are representative of populations of the European fox (Vulpes vulpes) in south-eastern Australia. When populations were regulated by density-dependent mechanisms in which sterile females did not participate, such as competition for resources among young animals or competition among fertile females for breeding sites or territories, then populations could increase in abundance for low and intermediate levels of imposed sterility. For other intraspecific regulatory mechanisms, such as competition for resources between all individuals, all levels of sterility were observed to reduce abundance. The population response was sensitive to (i) whether the survival of sterile adults was higher than that of fertile adults, (ii) whether animals could be sterilized before sexual maturity, and (iii) whether density dependence was modelled as a threshold process.

Animals↗
PubMed2001

Minimizing false-positives in universal newborn hearing screening: a simple solution.

BACKGROUND AND OBJECTIVES: The false-positive rates of previously reported universal newborn hearing screening (UNHS) programs range between 2.5% and 8%. Critics of UNHS programs have claimed that this rate is too high and might lead to a number of the negative effects produced by false-positive screening tests, namely emotional trauma, disease labeling, iatrogenesis from unnecessary testing, and increased expense in terms of time and money. We previously reported, based on some preliminary data, that as many as 80% of newborns who failed the initial hearing screen subsequently passed when they were retested the following day, before being discharged from the hospital. We now present the results of this intervention for our entire UNHS program during a 7-month period. METHODS: We analyzed data from 3142 non-neonatal intensive care unit infants screened with an automated auditory brainstem response at the Women's Hospital of Greensboro from November 1, 1999 to May 31, 2000. A protocol was developed wherein all infants who failed the initial UNHS were rescreened with another automated auditory brainstem response before hospital discharge. Data collected included pass/fail rates during the inpatient stay as well as follow-up data and risk factors for congenital hearing loss. RESULTS: Confirmed hearing loss occurred in 8 nonneonatal intensive care unit infants, a rate of 2.5/1000. Eighty percent of newborns who failed the initial hearing screen passed on rescreening before hospital discharge. This produced a false-positive rate of 0.8% and a corresponding positive predictive value of 24%. If inhospital rescreening had not occurred, our false-positive rate and positive predictive value would have been 3.9% and 6.1%, respectively. CONCLUSIONS: Our simple intervention of rescreening all infants who failed their initial UNHS before hospital discharge reduced the false-positive rate of UNHS to 0.8%. We suggest that this simple, inexpensive intervention should be instituted for all similar UNHS programs.

Audiometry, Evoked Response↗
PubMed2000

Periodic triggering of an inducible gene for control of a wild population.

A possible method of control for the management of wild populations consists of continual introgression of an inducible transgene by releasing transgenic individuals, with periodic exposure of the population to a trigger. Exposure to the trigger causes death or sterility in carriers of the transgene, but is otherwise benign. We investigate the effectiveness of various strategies for control. We show that suppression of the population density below any pre-specified level is possible using this technique. At the same time we show that too frequent or too efficient exposure to the trigger can select for non-transgenic genotypes at an intensity such that the population density will be largely unaffected by the trigger. Choices for management parameters can ensure that the latter scenario is avoided. We show that releasing individuals carrying the transgene at more than one locus facilitates density control.

Animals↗
PubMed2000

The false-positive in universal newborn hearing screening.

OBJECTIVES: Concern has been raised about the frequency and subsequent emotional effect of a false-positive result during universal newborn hearing screening (UNHS). This study describes: 1) the results of 1 UNHS program and a potential method to significantly reduce the false-positive rate, and 2) the effect a false-positive result has on lasting maternal anxiety toward their children as well as their views toward UNHS in general. METHODS: A retrospective analysis was conducted using data from 5010 infants screened with an automated auditory brainstem response (ABR) at the Women's Hospital of Greensboro (WHOG) from July 6, 1998 to June 30, 1999. In addition, a structured telephone survey was given to mothers of infants who had failed the initial hearing screen (stage 1) and who had completed an outpatient rescreen (stage 2). RESULTS: Confirmed hearing loss occurred in non-neonatal intensive care unit infants at a rate of 1.8/1000. A false-positive rate of 1.9% occurred during stage 1 of UNHS (screening before newborn discharge). We attribute this relatively low rate to rescreening of 51% of those newborns who failed the initial screen before hospital discharge. Eighty percent of these rescreened infants passed, thus needing no additional follow-up. If we had rescreened all infants before discharge, the false-positive rate would have approached.5%. Results of the survey were reassuring with regard to lasting emotional effects of false-positive tests. Only 9% of mothers said they "treated their child differently" before outpatient rescreening, and only 14% reported any lasting anxiety after their child passed the outpatient repeat screen. Although none reached statistical significance, potential risk factors for lasting anxiety include more educated mothers, lack of understanding of UNHS, and a false-positive result in both stage 1 and stage 2. Over 90% of all mothers believed that UNHS was a good idea. CONCLUSIONS: By rescreening all infants before hospital discharge, the false-positive rate of UNHS performed using automated ABR can be reduced to <1%. However, for the false-positive results that do occur, any long-lasting and detrimental emotional impact between mother and infant seems to be small and could be reduced even more with improved understanding about UNHS.

Anxiety↗
PubMed2000

In vitro susceptibility of Yersinia enterocolitica isolated from the oral cavity of swine.

Antimicrobial susceptibility of 181 (107 ail-harboring isolates and 74 non-ail-harboring) Yersinia enterocolitica isolates obtained from the oral cavity of swine was determined against 24 antimicrobial agents. All Y. enterocolitica isolates were susceptible to sulfamethoxazole/trimethoprim, enrofloxacin, aminoglycosides, and nitrofurantoin. Susceptibility to tetracycline appeared to vary by lot of origin. Isolates were resistant to sulfonamides (other than sulfamethoxazole/trimethoprim), penicillin, ampicillin, ticarcillin, cephalothin, macrolides, and tiamulin.

Animals↗
PubMed1999

The AB-180 circulatory support system: summary of development and plans for phase I clinical trial.

BACKGROUND: The AB-180 circulatory support system is a small, durable, efficient centrifugal pump with low thrombogenic potential. The device was designed to provide a fully implantable, left ventricular assist system for short-term support to address the issues of systemic anticoagulation, thrombus formation, infection, and cost. METHODS: Extensive bench and animal studies were performed to validate the mechanical integrity of the device and its functionality as an implant. RESULTS: These studies demonstrated anticoagulation requirements, established operating guidelines, incorporated safety systems, and demonstrated safety and efficacy. CONCLUSIONS: The AB-180 fulfills the stated goals on initial evaluation. A phase I human trial is underway.

Adult↗
PubMed1999

Effects of mitomycin C and carboplatin pretreatment on multidrug resistance-associated P-glycoprotein expression and on subsequent suppression of tumor growth by doxorubicin and paclitaxel in human metastatic breast cancer xenografted nude mice.

Overexpression of P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP), and several other proteins has been associated with development of multidrug resistance by cancer cells, which represents a significant obstacle to successful treatment by chemotherapy. We had previously demonstrated that a single noncytotoxic dose of mitomycin C (MMC), carboplatin, or one of several other DNA cross-linking agents suppressed mRNA expression of the mdr1 gene coding for Pgp, leading to a subsequent suppression of Pgp protein levels and a concomitant decrease in drug efflux. Pretreatment with MMC led to a 5- to 10-fold decrease in the ED50 for cell killing by a subsequent agent such as the Pgp substrate, doxorubicin, but did not affect killing by the non-Pgp substrate, cisplatin. In this study, we report that MMC and carboplatin each significantly suppressed Pgp protein levels in human MDA-MB-435 cells xenografted as solid tumors into the lateral mammary fat pads of female nude mice, with a similar time course as had previously been observed in cell culture. Pretreatment of mice with MMC or carboplatin 48-72 h prior to receiving either doxorubicin or paclitaxel caused a significantly greater reduction in tumor growth rate compared to either agent alone or the combination given simultaneously. These data suggest that a combination chemotherapy regimen consisting of a DNA cross-linking agent given to modulate the MDR phenotype, followed by a second cytotoxic agent, may be an effective treatment for human patients with de novo or late stage acquired multidrug-resistant malignancies.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

p53 gene mutations in multiple myeloma.

AIM: To assess whether p53 gene mutation is important in the pathogenesis and progression of multiple myeloma. METHODS: Thirty eight DNA samples (derived predominantly from bone marrow) obtained from 31 patients with multiple myeloma were examined for mutations in p53 exons 5-9 by polymerase chain reaction single strand conformation polymorphism. Twenty three samples were analysed at the time of diagnosis (one patient had plasma cell leukaemia), three in plateau phase, and 12 at relapse (one plasma cell leukaemia and one extramedullary relapse). RESULTS: One p53 mutation was detected in this group of patients (3.2%). This was seen in the diagnostic bone marrow sample of a 35 year old man with stage IIA disease and occurred in exon 6 as a result of a silent A to G transition at codon 213 (CGA-->CGG), a polymorphism that has been reported in about 3% of breast and lung tumours. CONCLUSIONS: p53 gene mutations are rare events in multiple myeloma and would seem to be of limited value as a prognostic factor.

Adult↗
PubMed1994

Cellular interactions of murine immune cells exposed to live Mycobacterium intracellulare, its whole lipid extract, and its serovar-specific glycopeptidolipid.

In this study we examined some of the immunological responses to Mycobacterium intracellulare and its lipid components. Our results indicate that infection with M. intracellulare can increase the expression of adhesion molecules, ICAM-1 and LFA-1, only at the site of injection (peritoneum). There was no change in the expression of these adhesion molecules in the lymphoid organs (thymus and spleen). Significant increases in the adhesion molecules were observed in the spleen cells incubated with the lipid derived from mycobacteria in the presence of concanavalin (Con A) compared to the Con A alone. The expression of the Thy 1.2 and Lyt-2 markers was not affected by the bacteria or their lipids. The results indicate a marked increase in the mitogenic response by the infected spleen cells removed at an early day. The blastogenic study also indicated that the lipids can reduce the mitogen-induced blastogenesis of spleen cells removed from M. intracellulare- and saline-injected mice; moreover, they suggested that the spleen cells removed from Listeria monocytogenes-infected mice can also be affected by mycobacterial lipids. This indicates a nonspecific effect by these lipids. The results suggest that the immunological response was contingent upon prior exposure of the mice to M. intracellulare, and also was dependent on whether the cells came from the peritoneal cavity or lymphoid organs.

Animals↗
PubMed1994

Influence of suspension on the oxidative burst by rat neutrophils.

The influence of spaceflight on the oxidative burst of neutrophils is not known. The present study was designed to evaluate the influence of antiorthostatic suspension, a ground-based modeling system designed to simulate certain aspects of weightlessness that occur after spaceflight, on the capacity of rat neutrophils to express the oxidative burst, an important host defense mechanism against microbial pathogens. Rats were suspended in whole body harnesses in the antiorthostatic orientation for a 3- or 7-day period. Control rats were suspended orthostatically or allowed to remain in vivarium cages without the attachment of any suspension materials. After suspension, peripheral blood was harvested and neutrophils were isolated by density gradient centrifugation. The enriched neutrophil preparations were stimulated with N-formyl-methionyl-leucine-phenylalanine and phorbol myristic acid to induce the oxidative burst. It was found that neutrophils isolated from suspended animals released the same levels of superoxide anion as did vivarium control animals that were not suspended, indicating that whole body suspension did not alter this aspect of rat neutrophil function.

Animals↗
PubMed1992

Reduction in tissue iron stores with a new regimen of continuous ambulatory intravenous deferoxamine.

A new regimen of 24-hr ambulatory continuous intravenous infusion of deferoxamine (CIV DFO) through central venous ports was instituted in nine patients aged (mean +/- SD) 22.4 +/- 5.8 years over a period of 15.7 +/- 7.3 months. Central venous infusion sites were changed weekly in the clinic, eliminating the necessity for reconstitution of DFO and needle insertion at home. Because CIV DFO could be interrupted only by medical personnel, patient compliance was documented accurately; patients administered 93.0% +/- 3.2% of CIV DFO prescribed. Mean urinary iron excretion on CIV DFO (66.8 +/- 50.4 mg/24 hr) was significantly greater than that quantitated during 12-hr equivalent-dose subcutaneous DFO infusions (23.4 +/- 18.3 mg/24 hr; P less than 0.025). Mean serum ferritin declined by 71% over the treatment period (P less than 0.005). This regimen confers the advantages of uninterrupted exposure to DFO, is associated with excellent patient compliance, and should be considered in any patient with severe iron overload and erratic compliance with DFO.

Adolescent↗
PubMed1992

Beta 2-glycoprotein 1 (beta 2GP1) enhances cardiolipin binding activity but is not the antigen for antiphospholipid antibodies.

Some investigators have reported that a serum protein, beta 2-glycoprotein 1 (beta 2GP1), either alone or in combination with negatively charged phospholipid, may be the antigen for anticardiolipin (aCL) antibodies. To examine these reports further, ELISA tests, inhibition experiments, Ouchterlony and Western blot techniques were used to examine anticardiolipin binding to beta 2GP1. Sera from patients with the antiphospholipid syndrome (APS) and syphilis were studied, as well as whole IgG immunoglobulin and affinity purified (a.p.) IgG aCL antibodies. Results showed no binding of aCL antibodies to beta 2GP1 in the absence of cardiolipin. beta 2GP1 caused enhanced binding of aCL antibodies to cardiolipin, but this enhancement was not observed in inhibition experiments. Binding to cardiolipin occurred in the absence of beta 2GP1. Enhancement of cardiolipin binding activity by beta 2GP1 was observed for APS, but not for syphilis. We conclude that beta 2GP1 is not the antigen for aCL antibodies, nor is it likely that the antibody recognizes shared beta 2GP1-cardiolipin epitopes. Instead, this protein may make cardiolipin more available for aCL binding on solid surfaces by some yet undefined mechanism. This effect may not extend to aqueous suspensions.

Antibodies, Anticardiolipin↗
PubMed1992

Patients' acceptance of monitoring fetal movement. A randomized comparison of charting techniques.

An active fetus is reassuring to both the woman and her obstetrician. Numerous techniques of charting fetal movement have been shown to assist the clinician in caring for the high-risk patient. Patients' compliance with daily monitoring is an important clinical issue, and little information exists on the fetal movement record most preferred by the patient. A comparative study evaluated patients' acceptance of three commonly used charts. The 85 enrollees were given the different charts in a random manner and questioned at the next office visit. All the patients expressed approval of the concept and a lack of anxiety about such monitoring, complied with our instructions and returned the completed records. The neonatal outcomes were favorable with all the charting techniques in our antenatal fetal surveillance plan. The "count-to-10" method was rated most preferred in 95.3% of the cases. The reasons cited included convenience and less time needed to complete the recording. The mean time to complete this record was 19.7 +/- 22.9 minutes rather than one or more hours, as with the other charting methods. The results of this randomized investigation show the simple and rapid count-to-10 method to be the most acceptable charting technique to our patients for monitoring fetal movement.

Female↗
PubMed1990

Uterine and fetal Doppler flow changes from a single dose of a long-acting intranasal decongestant.

Oxymetazoline, an alpha-adrenergic agent, is the active vasoconstrictor in long-acting intranasal decongestants. This investigation studied the effects of oxymetazoline on the maternal and fetal circulations. Twelve healthy gravid patients in the third trimester (27-39 weeks) underwent flow velocity measurements by the same sonographer using a pulsed Doppler system (ATL Ultramark 4 machine). Maternal and fetal indices were recorded 15 minutes before dosing, immediately thereafter, and at 15-minute intervals during the first 2 hours after the drug was given. No significant changes were found in either the maternal blood pressures or pulse rates. Blood flow velocities did not change significantly from baseline for the uterine arcuate artery, fetal aorta, or umbilical artery circulations. In no case did absolute blood flow velocity decrease significantly or systolic/diastolic ratios elevate to worrisome values. For uncomplicated pregnancies, we conclude there are no significant acute changes in the maternal and fetal circulations after a single dose of intranasal oxymetazoline.

Administration, Intranasal↗