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Biomedical subjects

L Wallace

Publications and source records attributed to L Wallace.

At least 37 records · Page 2Linked to original sources
PubMed1999

Topical DMSO treatment for pegylated liposomal doxorubicin-induced palmar-plantar erythrodysesthesia.

PURPOSE: Chemotherapeutic regimens that utilize fluorouracil, cytarabine, and doxorubicin have been shown to cause a dermatologic syndrome known as hand-foot syndrome, or palmar-plantar erythrodysesthesia syndrome (PPES). Pegylated liposomal doxorubicin has proven effective in the treatment of AIDS-related Kaposi's sarcoma, ovarian cancer refractory to platinum and paclitaxel therapies, and metastatic breast cancer. In a study of the treatment of refractory epithelial cell ovarian cancers with lipozomal doxorubicin utilizing intravenous doses of 50 mg/m(2) every 3 weeks, grade 3 PPES was observed in 29% of patients (10/35) and required dose reductions and/or dose delay after a median of three therapy cycles. METHODS: Current methods to prevent pegylated liposomal doxorubicin-induced PPES include dose reduction, lengthening of the drug administration interval and ultimately, drug withdrawal. Topical 99% dimethylsulfoxide (DMSO) also has shown strong activity in treating tissue extravasation reactions during intravenous administration of doxorubicin. RESULTS: Two patients undergoing chemotherapy with pegylated liposomal doxorubicin, 50 mg/m(2) every 4 weeks, developed grade 3 PPE after three cycles. Their PPES resolved over a period of 1 to 3 weeks while receiving topical 99% DMSO four times daily for 14 days. CONCLUSIONS: While these results are promising, patients must be treated in a prospective study of this topical DMSO formulation to definitively document its therapeutic efficacy.

Administration, Topical↗
PubMed1998

Aflatoxin B1 and sulphobromophthalein binding to the dimeric human glutathione S-transferase A1-1: a fluorescence spectroscopic analysis.

The binding interactions between dimeric human class alpha glutathione S-transferase A1-1 (GST A1-1) and aflatoxin B1 or sulphobromophthalein (BSP) were characterised. Aflatoxin B1 binds to GST A1-1 with a stoichiometry of 1.1 mol/mol of dimeric enzyme. The binding interaction, which can be described by a hyperbolic saturation isotherm (Kd = 8+/-2 microM), does not induce major structural changes in the enzyme, nor does it inhibit enzymatic activity. The average distance between the single tryptophan residue (Trp20) of GST A1-1 and protein-bound aflatoxin B1 was calculated to be 22.7 A by means of fluorescence resonance energy transfer. The aflatoxin-binding region, according to this calculated distance, was determined to be located in the dimer interface cleft near the crystallographic two-fold axis. Hill-plot analyses suggest that a positive co-operative interaction exists between BSP and the dimeric GST A1-1 (h = 1.6+/-0.1; K' = 14+/-0.6 microM). The binding of BSP induces a conformational change in the enzyme which is accompanied by a decrease in the molecular flexibility and in the solvent-accessible properties of the enzyme's Trp20 residue. Site-directed mutagenesis of Trp20 (Trp20-->Phe) confirms that this residue is situated in the binding environment and although it is not essential for BSP binding, it is involved in the interaction. Furthermore, the structural change associated with BSP binding alters the hyperbolic character of the glutathione saturation curve. This indicates that there may also be a cooperative interaction between glutathione and BSP or that BSP binding induces asymmetric functioning of the two enzyme subunits so that they become unequal in catalytic activity.

Aflatoxin B1↗
PubMed1998

Nocturnal hemodialysis (NHD) adapted to the in-centre setting--a pilot study.

Nocturnal hemodialysis has proven to be an effective and safe modality with many benefits. Using NHD parameters, two in-centre conventional hemodialysis (CHD) patients participated in a three-week in-hospital trial to test the viability of an in-hospital nocturnal hemodialysis (NHD) program. One RN was responsible for the initiation and monitoring of all treatments. In order to objectively measure results, we maintained a daily log detailing alarm situations, response time for both technical and medical support, and required interventions. Patient and staff comments were recorded daily. Miscellaneous problems were also documented. Both patients were given quality of life questionnaires and patient satisfaction surveys pre- and post-trial. Occasionally, difficulties with machine and vascular access problems were encountered. Results revealed that subjectively, both patients felt much better on NHD when compared to CHD, however they found that their personal lives were adversely affected by their absence from home. Upon completion of the trial, the accumulated data was analyzed and recommendations were made. It was decided that a staff/patient ratio of 1:3 would be safe providing that the physical environment allowed the RN to oversee all functions. Due to patient dissatisfaction with treatments six nights per week, it was suggested that flexibility with patient scheduling was essential. However, it was agreed that six nights per week would be advantageous within a chronic care facility offering hemodialysis therapy. To ensure complete medical coverage, renal fellow integration within the nocturnal project was recommended. In conclusion, we feel that the adaptation of NHD to the in-centre setting is viable with the appropriate patient population and physical environment.

Appointments and Schedules↗
PubMed1997

Water on the sun: line assignments based on variational calculations.

The infrared spectrum of hot water observed in a sunspot has been assigned. The high temperature of the sunspot (3200 K) gave rise to a highly congested pure rotational spectrum in the 10-micrometer region that involved energy levels at least halfway to dissociation. Traditional spectroscopy, based on perturbation theory, is inadequate for this problem. Instead, accurate variational solutions of the vibration-rotation Schrödinger equation were used to make assignments, revealing unexpected features, including rotational difference bands and fewer degeneracies than anticipated. These results indicate that a shift away from perturbation theory to first principles calculations is necessary in order to assign spectra of hot polyatomic molecules such as water.

Chemical Phenomena↗
PubMed1997

Na(+)-dependent and -independent Cl-/HCO-3 exchange mediate cellular HCO3- transport in cultured human intrahepatic bile duct cells.

Biliary epithelial cells (cholangiocytes) modulate bile fluidity and alkalinity absorbing and/or secreting fluid and electrolytes, particularly HCO3- and Cl-. Mechanisms responsible for transepithelial H+/HCO3- secretion in human cholangiocytes are largely unknown. Human cholangiocytes isolated by enzymatic digestion and immunomagnetic purification from normal liver tissue obtained from reduced grafts used for pediatric liver transplantation were cultured in the presence of human hepatocyte growth factor. Maintenance of cholangiocyte phenotypic features was assessed using markers such as cytokeratin 19, gamma-glutamyltranspeptidase, vimentin, factor VIII-related antigen, desmin, epithelial membrane antigen (EMA), and human epithelial antigen (HEA) 125. Intracellular pH (pHi) transients were measured microfluorimetrically 2'7'-Bis(2-carboxyethyl)-5,6, carboxyfluorescein-acetossimethylester (BCECF). In the absence of HCO3-, pHi recovery from an intracellular acid load (ammonia pre-pulse technique) was Na(+)-dependent and amiloride-inhibitable. No Na(+)-independent recovery was recorded even after stimulation with agents raising intracellular cyclic adenosine monophosphate (cAMP) concentrations. In the presence of HCO3-, recovery from an intracellular acid load required Na+, but was only partly inhibited by amiloride. In these conditions H+ extrusion was inhibited by 4,4-diisothiocyan atostilben-2,2-disulfonic acid (DIDS) and by intracellular Cl- depletion. Acute removal of extracellular Cl induced a pHi alkalinization that was inhibited by DIDS. pHi recovery from an intracellular alkaline load (isohydric CO2 changes) was Cl(-)-dependent and DIDS-inhibitable. Administration of agents raising intracellular cAMP concentrations increased both Na(+)-dependent and Na(+)-independent Cl-/HCO-3 exchange activity. Stimulation of Cl-/HCO3- exchange activity was not prevented by the Cl- channel inhibitor 5'-nitro-2(2)-phenylpropyl-amino-benzoate(NPPB). In conclusion, human cholangiocytes possess two acid extruders (Na+/H+exchanger and Na(+)-dependent Cl-/HCO3- exchange) and an acid loader (Cl-/HCO3- exchange), whereas no evidence was found for cAMP activated H(+)-ATPase. Bicarbonate influx is thus mainly mediated by Na-dependent Cl-/HCO3- exchange, whereas Na+:HCO-3 cotransport is not active in the physiological range of pHi. Stimulation of Na(+)-independent Cl-/HCO3- exchanger by cAMP does not require activation of Cl- conductances. These mechanisms may underlay hormone-regulated biliary HCO3- secretion in the human biliary tree.

Antiporters↗
PubMed1997

High-Temperature Rotational Transitions of Water in Sunspot and Laboratory Spectra

Assignments are presented for spectra of hot water obtained in absorption in sunspots (T approximately 3000&deg;C and 750 </= nu; </= 1010 cm-1) and in emission in the laboratory (T approximately 1550&deg;C and 370 </= nu; </= 930 cm-1). These assignments are made using variational nuclear motion calculations based on a high-level ab initio electronic surface, with allowance for both adiabatic and nonadiabatic corrections to the Born-Oppenheimer approximation. Some 3000 of the 4700 transitions observed in the laboratory spectrum are assigned as well as 1687 transitions observed in the sunspot spectrum. All strong lines are now assigned in the sunspot measurements. These transitions involve mostly high-lying rotational levels within the (0,0,0), (0,1,0), (0,2,0), (1,0,0), and (0,0,1) vibrational states. Transitions within the (0,3,0), (0,4,0), (1,1,0), (0,1,1), (0,2,1), (1,1,1), (1,2,0), and (1,0,1) states are also assigned. For most bands the range of Ka values observed is significantly extended, usually doubled. New features observed include numerous cases where the closely degenerate levels JKaKc and JKaKc+1 with high Ka are split by Coriolis interactions. Comparisons are made with the recent line list of Partridge and Schwenke (1997, J. Chem. Phys. 106, 4618). Copyright 1997 Academic Press. Copyright 1997Academic Press

Journal Article↗
PubMed1997

Effect of pertussis toxin injected into the ventral tegmental area on amphetamine-induced Fos protein in the nucleus accumbens.

Amphetamine produces an enhanced locomotor stimulatory response in animals injected with pertussis toxin into the ventral tegmental area. This response is dependent on the activation of D1 receptors in the nucleus accumbens. The immediate early gene, c-Fos, has been used as a cellular marker for increases in dopamine neurotransmission in the nucleus accumbens. The purpose of the present study was to determine whether the administration of pertussis toxin into the ventral tegmental area results in an increased ability of amphetamine to induce Fos-positive immunoreactivity in the nucleus accumbens. Amphetamine (1 mg/kg and 2 mg/kg IP) produced a greater number of Fos-positive cells in the nucleus accumbens of pertussis toxin-treated animals as compared to vehicle-treated controls. However, the increase in Fos immunoreactivity at the higher amphetamine dose was not associated with a corresponding increase in locomotor activity. These data suggest that amphetamine produces an enhanced increase in dopamine neurotransmission in the nucleus accumbens of pertussis toxin-treated animals, resulting in an increased induction of Fos-related antigens.

Amphetamine↗
PubMed1997

Ambient air concentrations of fine (PM2.5) manganese in U.S. national parks and in California and Canadian cities: the possible impact of adding MMT to unleaded gasoline.

The October 1995 court decision allowing Ethyl Corporation to offer methylcyclopentadienyl manganese tricarbonyl (MMT) for sale to refiners for introduction into unleaded gasoline as an octane enhancer is likely to result in increased fine (PM2.5) manganese (Mn) concentrations in ambient air. Concern exists regarding possible health effects. In this paper, recent fine Mn concentrations in three monitoring networks and one U.S. Environmental Protection Agency (EPA) study of personal exposure are analyzed. One network consists mainly of rural sites in national parks in the United States, a second consists mainly of urban sites in California, and the third consists mainly of urban sites in Canada where MMT has been used for a number of years. During the late 1980s and early 1990s, mean ambient concentrations ranged from 1 ng/m3 in the mostly rural network to 3 ng/m3 in the mostly urban California network to 12 ng/m3 in the MMT-impacted Canadian network. Several lines of evidence suggested that some of the fine Mn observed in the United States during the 1986-1992 period was contributed by automobiles using leaded gasoline, for which MMT was a registered fuel additive. However, the near-disappearance of leaded gasoline has resulted in a very small portion of fine Mn being attributed to automobiles in the years since 1992. A source apportionment analysis suggested that crustal contributions to ambient fine Mn are on the order of 1-2 ng/m3 in both the United States and Canada.

Air Pollutants↗
PubMed1997

Empirical approaches for the investigation of toxicant-induced loss of tolerance.

It has been hypothesized that sensitivity to low-level chemical exposures develops in two steps: initiation by an acute or chronic chemical exposure, followed by triggering of symptoms by low levels of previously tolerated chemical inhalants, foods, or drugs. The Working Group on Toxicant-induced Loss of Tolerance has formulated a series of research questions to test this hypothesis: Do some individuals experience sensitivity to chemicals at levels of exposure unexplained by classical toxicological thresholds and dose-response relationships, and outside normally expected variation in the population? Do chemically sensitive subjects exhibit masking that may interfere with the reproducibility of their responses to chemical challenges? Does chemical sensitivity develop because of acute, intermittent, or continuous exposure to certain substances? If so, what substances are most likely to initiate this process? An experimental approach for testing directly the relationship between patients' reported symptoms and specific exposures was outlined in response to the first question, which was felt to be a key question. Double-blind, placebo-controlled challenges performed in an environmentally controlled hospital facility (environmental medical unit) coupled with rigorous documentation of both objective and subjective responses are necessary to answer this question and to help elucidate the nature and origins of chemical sensitivity.

Controlled Clinical Trials as Topic↗
PubMed1996

Role of dopaminergic mechanisms in the stimulatory effects of MK-801 injected into the ventral tegmental area and the nucleus accumbens.

The bilateral administration of 10 micrograms of (+)MK-801, but not (-)MK-801, into either the VTA or the N.Ac. stimulated locomotor activity. The stimulation induced by (+)MK-801 at both sites was inhibited by reserpine (5 mg/kg, SC) and the D1 antagonist, SCH 23390 (0.1 mg/kg, SC). Eticlopride (0.03 mg/kg, SC), a D2 antagonist, inhibited the stimulation produced by MK-801 in the VTA but not in the N.Ac. Baclofen (32 ng), a GABAB receptor agonist, injected into the VTA inhibited the stimulatory response to MK-801 injected systemically, into the VTA, or into the N.Ac., but did not significantly inhibit spontaneous locomotion or the stimulatory response to apomorphine (5 mg/kg, SC). These observations suggest that the stimulatory effects of MK-801 in the VTA and the N.Ac. are dependent on endogenous dopamine. In addition, the effects produced by MK-801 injected into the VTA closely resemble those produced by the systemic administration of low doses of MK-801, suggesting that this is the primary site of action of MK-801.

Adrenergic Uptake Inhibitors↗
PubMed1996

Slow nocturnal home hemodialysis at the Wellesley Hospital.

To alleviate the overcrowding of in-center hemodialysis (HD) facilities, we have developed slow nocturnal home hemodialysis (SNHHD), an innovative form of renal replacement therapy. SNHHD is performed 5 to 7 nights/week for 8 hours, during sleep, with a blood flow of 300 mL/min and a dialysate flow of 100 mL/min. The vascular access is by means of the Uldall-Cook catheter, which allows for easy patient access with low infection rates. Special precautions were taken to prevent accidental disconnection during sleep. Dialysis functions were monitored via a modem from the patient's home to the SNHHD center and have proven valuable in increasing patient confidence. The removal of urea, phosphate, and B2 microglobulin (B2M) during 1 week of SNHHD greatly exceeds that of thrice weekly conventional HD. Five patients have completed training and have been successfully performing SNHHD for 6 to 16 months. All patients have discontinued phosphate binders and increased dietary phosphate intake. Four out of five patients report sleeping soundly and experience greatly increased energy and stamina. Repeated in situ reuse of the dialyzer and the blood lines will reduce the patients work and make SNHHD a very inexpensive modality.

Adult↗
PubMed1996

Indoor particles: a review.

This paper reviews studies of particle concentrations and sources in homes and buildings. Three major studies of indoor and outdoor concentrations in U.S. homes are summarized in detail and compared. A number of smaller studies in homes are also briefly summarized. One study of 38 buildings and several smaller studies of buildings are also reviewed. All major studies found that an important indoor source of fine and coarse particles was cigarette smoking, with estimated increases in homes with smokers ranging from 25 to 45 micrograms/m3 PM2.5. Several studies identified cooking as a second important source. All of the three major studies found a substantial portion of indoor particles to be due to unexplained indoor sources, suggesting a topic for future research. One study also found a large unexplained increase in personal exposure to PM10 compared to concurrent indoor or outdoor concentrations--the so-called "personal cloud," a second topic for further research. The impact of outdoor air particles on indoor concentrations was considered. Equilibrium mass balance models indicate that this is a function of the penetration P through the building envelope, the air exchange rate a, and the particle decay rate k. EPA's PTEAM Study provided an estimate for k of 0.39 h-1 for fine particles and 1.01 h-1 for coarse particles. Two studies suggest that P = 1 for PM10. Using these results, the fraction of outdoor air PM2.5 and PM10 particles found indoors at a given air exchange rate can be calculated. The protective effect of reducing air exchange rates during periods of high outdoor particle pollution can thus be quantified.

Air Pollution, Indoor↗
PubMed1996

Environmental exposure to benzene: an update.

During the 1990s, several large-scale studies of benzene concentrations in air, food, and blood have added to our knowledge of its environmental occurrence. In general, the new studies have confirmed the earlier findings of the U.S. Environmental Protection Agency Total Exposure Assessment Methodology (TEAM) studies and other large-scale studies in Germany and the Netherlands concerning the levels of exposure and major sources. For example, the new studies found that personal exposures exceeded indoor concentrations of benzene, which in turn exceeded outdoor concentrations. The new studies of food concentrations have confirmed earlier indications that food is not an important pathway for benzene exposure. The results of the National Health and Nutrition Examination Survey on blood levels in a nationwide sample of 883 persons are in good agreement with the concentrations in exhaled breath measured in about 800 persons a decade earlier in the TEAM studies. Major sources of exposure continue to be active and passive smoking, auto exhaust, and driving or riding in automobiles. New methods in breath and blood sampling and analysis offer opportunities to investigate short-term peak exposures and resulting body burden under almost any conceivable field conditions.

Air Pollutants↗
PubMed1996

Breath measurements as volatile organic compound biomarkers.

A brief review of the uses of breath analysis in studies of environmental exposure to volatile organic compounds (VOCs) is provided. The U.S. Environmental Protection Agency's large-scale Total Exposure Assessment Methodology Studies have measured concentrations of 32 target VOCs in the exhaled breath of about 800 residents of various U.S. cities. Since the previous 12-hr integrated personal air exposures to the same chemicals were also measured, the relation between exposure and body burden is illuminated. Another major use of the breath measurements has been to detect unmeasured pathways of exposure; the major impact of active smoking on exposure to benzene and styrene was detected in this way. Following the earlier field studies, a series of chamber studies have provided estimates of several important physiological parameters. Among these are the fraction, f, of the inhaled chemical that is exhaled under steady-state conditions and the residence times. tau i in several body compartments, which may be associated with the blood (or liver), organs, muscle, and fat. Most of the targeted VOCs appear to have similar residence times of a few minutes, 30 min, several hours, and several days in the respective tissue groups. Knowledge of these parameters can be helpful in estimating body burden from exposure or vice versa and in planning environmental studies, particularly in setting times to monitor breath in studies of the variation with time of body burden. Improvements in breath methods have made it possible to study short-term peak exposure situations such as filling a gas tank or taking a shower in contaminated water.

Biomarkers↗
PubMed1996

Evaluation of the effectiveness of a pavement stencil in promoting safe behavior among elementary school children boarding school buses.

OBJECTIVE: The majority of school bus-related fatalities among children attending elementary school in the United States occur as children board or alight from buses. Injuries occur during boarding when children enter the street and are struck by buses or other vehicles. This study evaluated the effectiveness of a stencil in the shape of a school bus applied to the pavement at a bus stop in improving safe behaviors at bus stops. Specifically, we assessed the frequency of children running toward the bus as it approached or entered the street. METHODS: Elementary school bus stops with similar roadways, traffic profiles, and numbers of children boarding participated in the study. Stops were randomly assigned to an intervention group, in which children were instructed to remain within a safe area during boarding that was demarcated by a pavement stencil, or an education-only group, in which the safe area was demarcated by some existing environmental feature. Both groups received education about safe boarding procedures. Observers rated behavior at each stop daily for 5 consecutive weeks. Data were analyzed as bivariate odds of any unsafe behavior in the education-only group. RESULTS: One hundred forty-five observations from seven bus stops with stencils and 174 daily observations from six education-only stops were completed. Observations of children in the education-only group were twice as likely to show unsafe behavior while waiting (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.3-3.6) and during boarding (OR, 2.1; 95% CI, 1.2-3.9). ORs were significantly higher in the education-only group for boys, girls, and children in grades 4 through 6. When no adult was present, there was a greater likelihood of unsafe behavior among all children in the education-only group while waiting (OR, 16.1; 95% CI, 3.9-72.4) and during boarding (OR, 15.0; 95% CI, 3.2-81.4). The presence of an adult at the stop did not have an independent effect on behavior. Children at education-only stops located on roadways with high traffic volume were more likely to engage in unsafe behavior while waiting (OR, 8.0; 95% CI, 3.8-17.3) and during boarding (OR, 4.9; 95% CI, 2.2-11.0). No differences were observed during boarding between stencil and education-only groups when 10 or more children were at the stops. CONCLUSION: The pavement stencil, when accompanied by education about safe boarding, may represent a cost-effective approach to reducing unsafe behavior at bus stops by children of elementary school age.

Accidents, Traffic↗