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Drug resistance and gene amplification potential regulated by transforming growth factor beta 1 gene expression.

Transforming growth factor beta 1 (TGF-beta 1) regulates a multitude of diverse biological functions in mammalian cells, and there is good evidence that aberrant expression of this growth factor can play an important role in mechanisms of malignant progression. We show that a TGF-beta 1-overexpressing mouse 10T1/2 cell line transfected with a TGF-beta 1 sequence that allows the synthesis of bioactive growth factor exhibits reduced sensitivity to the cytotoxic effects of the drug N-(phosphonacetyl)-L-aspartate (PALA) in colony-forming experiments. Furthermore, six independent 10T1/2 TGF-beta 1-transfected cell lines containing TGF-beta 1 gene expression under the control of a zinc sulfate-responsive metallothionein promoter were selected. In all cases, sensitivity to PALA cytotoxic effects was significantly reduced when cells were cultured under conditions that led to elevated levels of TGF-beta 1 gene expression when compared to cells containing basal levels of this growth factor. Fluctuation analysis to determine the rate of PALA resistance was performed with several TGF-beta 1-transfected cell lines in which growth factor expression was regulated by the metallothionein promoter. We observed significantly higher rates of PALA resistance/cell/generation in cell populations expressing high levels of TGF-beta 1 than in the same cells expressing relatively low levels of this growth factor. The only mechanism known for PALA resistance in mouse cells involves the amplification of the gene coding for the protein target of PALA, CAD, a multifunctional polypeptide containing carbamyl phosphate synthetase, aspartate transcarbamylase, and dihydroorotase. Southern blot analysis of colonies that survived normally cytotoxic concentrations of PALA exhibited CAD gene amplification. In total, these observations indicate that aberrant expression of TGF-beta 1 gene expression decreases the genetic stability of 10T1/2 cells, leading to increased rates of drug resistance and elevated gene amplification potential. The results of this study indicate a new malignancy related function for TGF-beta 1 alterations and suggest a novel role for aberrant expression of this growth factor in mechanisms of drug resistance and tumor progression.

Animals↗

Genetic instability induced by the tumor microenvironment.

The tumor microenvironment is characterized by regions of fluctuating hypoxia, low pH, and nutrient deprivation. To determine the genetic consequences of growth under these conditions, we used a tumorigenic cell line carrying a recoverable, chromosomally based lambda phage shuttle vector designed to report mutations without the need for genetic selection of mutant cells. The cells were grown in parallel either in culture or as tumors in nude mice. The frequency of mutations arising in cells within the tumors was found to be 5-fold higher than that in otherwise identical cells grown in culture. A distinct pattern of mutation was also seen, with significantly more deletions and transversions in the tumors than in the cell cultures. Furthermore, exposure of the cultured cells to hypoxia produced an elevated mutation frequency and a mutation pattern similar to that seen in the tumors. These results indicate that the conditions within solid tumors are mutagenic and suggest that a fundamental mechanism of tumor progression in vivo is genetic instability induced by the tumor microenvironment.

Animals↗

Modified thoracic impedance plethysmography to monitor sleep apnea syndromes.

BACKGROUND AND PURPOSE: In order to identify sleep disorders by thoracic impedance plethysmography (TIP), we propose several new techniques: the application of an adaptive filter, a scaled Fourier linear combiner (SFLC) to eliminate cardiac-derived fluctuation in the impedance waveform, and the use of heart rate variability (HRV) to ascertain whether the airflow is obstructed. PATIENTS AND METHODS: Laboratory simulation experiments on four healthy individuals and actual overnight measurements on five patients with sleep disorders were carried out. Amplified thoracic impedance change (DeltaZ), ECG, a phonocardiograph, a pneumotachograph and a standard polysomnograph were recorded. The SFLC was applied to DeltaZ to selectively extract the cardiac-synchronous component (DeltaZ(CSC)), and the remainder of the waveform (DeltaZ(REM)) was low-pass filtered to estimate the waveform driven by respiration. The HRV was divided into respiratory synchronous (HRV(R)) and low frequency (HRV(L)) components. RESULTS: The SFLC could drastically extract DeltaZ(CSC) from DeltaZ and thereby demonstrate a DeltaZ(REM) pattern quite similar to the flow-volume curve of the pneumotachograph. Central sleep apnea could be identified as the cessation of DeltaZ(REM) and concomitant attenuation of HRV(R). Obstructive sleep apnea could be identified as the maintenance of rhythmic but attenuated variations of DeltaZ(REM) accompanied by asynchronous fluctuation of HRV(R) against DeltaZ(REM). Central hypopnea could be identified as a normal but attenuated waveform in both DeltaZ(REM) and HRV(R). A large fluctuation in HRV(L) was observed during repetitive appearances of apnea/hypopnea in the nocturnal experiments. CONCLUSION: The modified TIP together with HRV provides a superior tool for accurate and convenient definition of sleep apnea syndromes.

Heart Rate↗

Stress and growth response of juvenile crayfish to rhythmic and arrhythmic temperature fluctuations.

Growth, molting, and survival of juvenile crayfish, Procambarus a. acutus, were recorded under constant and variable temperature regimes. Crayfish, were exposed to four rhythmic regimes: Constants temperatures of 10, 17.5, and 25 degree C, and a daily square-wave cyclic regime of 10 to 25 degree C (mean = 17.5 degree C); and to one arrhythmic temperature regime: A daily square-wave acrylic regime varying within 10 to 25 degree C limits (mean = 17.8 degree C). The direction and magnitude of temperature changes in the acyclic variable temperature chamber were selected randomly to make temperature changes unpredictable within the specified range. Rhythmic and arrhythmic temperature regimes had different effects on growth, molting, and survival of crayfish. Growth under both variable regimes was similar to growth at a constant temperature (17.5 degree C) equal to the mean of the variable regimes. Molt frequency was directly related to temperature. Growth rates approximately paralleled changes in the adjusted molt rate for each regime. Mortality under variable regimes approximated mortality at a constant temperature (25 degree C) equal to the upper extreme of the variable regimes. The cyclic regime tended to be less optimal for growth and survival than the acyclic regime, possibly because of differences in average daily temperature fluctuations and relative time spent at temperature extremes.

Animals↗

The mechanism of glycerol conduction in aquaglyceroporins.

BACKGROUND: The E. coli glycerol facilitator, GlpF, selectively conducts glycerol and water, excluding ions and charged solutes. The detailed mechanism of the glycerol conduction and its relationship to the characteristic secondary structure of aquaporins and to the NPA motifs in the center of the channel are unknown. RESULTS: Molecular dynamics simulations of GlpF reveal spontaneous glycerol and water conduction driven, on a nanosecond timescale, by thermal fluctuations. The bidirectional conduction, guided and facilitated by the secondary structure, is characterized by breakage and formation of hydrogen bonds for which water and glycerol compete. The conduction involves only very minor changes in the protein structure, and cooperativity between the GlpF monomers is not evident. The two conserved NPA motifs are strictly linked together by several stable hydrogen bonds and their asparagine side chains form hydrogen bonds with the substrates passing the channel in single file. CONCLUSIONS: A complete conduction of glycerol through the GlpF was deduced from molecular dynamics simulations, and key residues facilitating the conduction were identified. The nonhelical parts of the two half-membrane-spanning segments expose carbonyl groups towards the channel interior, establishing a curve-linear pathway. The conformational stability of the NPA motifs is important in the conduction and critical for selectivity. Water and glycerol compete in a random manner for hydrogen bonding sites in the protein, and their translocations in single file are correlated. The suggested conduction mechanism should apply to the whole family.

Amino Acid Motifs↗

Deep brain stimulation in neurologic disorders.

Deep brain stimulation (DBS) is an effective surgical therapy for well-selected patients with medically intractable Parkinson's disease (PD) and essential tremor (ET). The purpose of this review is to describe the success of DBS in these two disorders and its promising application in dystonia, Tourette Syndrome (TS) and epilepsy. In the last 10 years, numerous short- and intermediate-term outcome studies have demonstrated significant relief to patients with PD and ET. A few long-term follow-up studies have also reported sustained benefits. When successful, DBS greatly reduces most of parkinsonian motor symptoms and drug-induced dyskinesia, and it frequently improves patients' ability to perform activities of daily living with less encumbrance from motor fluctuations. Quality of life is enhanced and many patients are able to significantly reduce the amount of antiparkinsonian medications required to still get good pharmacological benefit. Overall, adverse effects associated with DBS tend to be transient, although device-related and other postoperative complications do occur. DBS should be considered the surgical procedure of choice for patients who meet strict criteria with medically intractable PD, ET and selected cases of dystonia.

Clinical Trials as Topic↗

Differences in basal and stress-induced HPA regulation of wild house mice selected for high and low aggression.

Male wild house mice, selected for short (SAL) and long (LAL) attack latency, show distinctly different behavioral strategies in coping with environmental challenges. In this study, we tested the hypothesis that this difference in coping style is associated with a differential stress responsiveness of the hypothalamic-pituitary-adrenal (HPA) system. SAL rather than LAL mice showed a clear fluctuation in circulating corticosterone concentrations around the circadian peak with significantly higher levels in the late light phase. LAL mice showed lower basal ACTH levels and higher thymic and spleen weights compared to SAL. Under basal conditions, glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) mRNA in the hippocampus and corticotropin-releasing hormone (CRH) mRNA in the paraventricular nucleus of the hypothalamus were not different between the two lines. Forced swimming for 5 min induced high immobility behavior in LAL mice which was associated with an enhanced and prolonged corticosterone response as compared to SAL, while absolute ACTH levels did not differ. In addition, LAL mice showed an increase in hippocampal MR mRNA (but not GR) and hypothalamic CRH mRNA at 24 h after forced swimming. In conclusion, a genetic trait in coping style of wild house mice is associated with an idiosyncratic pattern of HPA activity, and greater responsiveness of physiological and molecular stress markers in LAL mice. In view of the profound differences in behavioral traits and stress system reactivity, these mouse lines genetically selected for attack latency present an interesting model for studying the mechanism underlying individual variation in susceptibility to stress-related psychopathology.

Acute Disease↗

The temporal structure of S phase.

DNA synthesis in the S phase of V79 and CHO Chinese hamster cells was examined in detail using an automated system for selection and subculturing of mitotic cells and four different assays for DNA synthesis. Flow microfluorometric (FMF) analysis showed that the selected populations were highly synchronous with few noncycling cells. In CHO cells changes in mean and modal fluorescence in the FMF suggested that DNA content increased in a saltatory fashion with 10-20% of the DNA replicated in early S, 40% in mid S, and 40-50% in late S. Pulse labeling and acid precipitation revealed a repeatable pattern of fluctuations in the rate of isotope incorporation with the maximum rate occurring late in S both V79 and CHO. Autoradiography proved to be the best means of accurately determining the beginning of S phase. Cumulative labeling from mitosis to points in S exaggerated the differences in rate between early and late S, so that significant DNA synthesis in early S might easily be overlooked using this method. In CHO cells DNA-specific fluorescence by the Kissane and Robins assay supported the isotopic incorporation data and the FMF analyses by exhibiting a stepwise increase. In V79 cells, S phase lasts only 5 or 5.5 hr, and consequently the mid S and late S steps in fluorescence are compressed. In V79, greater than 80% of the increase in DNA-specific fluorescence occurred between 4.5 and 7 hr after mitotic selection. In both cell lines, fluorescence in early S phase frequently increased transiently to maximum and then decreased.

Animals↗

Fetal hemoglobin synthesis in culture of early erythroid precursors (BFU-E) from the blood of normal adults.

BFU-E from the blood of 14 normal adults have been grown by the plasma clot technique. The hemoglobins synthesized in burst colonies were purified from other proteins by affinity chromatography on Sepharose-haptoglobin. The radioactivity incorporated in the globin chains was estimated by CM-cellulose chromatography in urea. The number of bursts scored at the 14th day of culture fluctuated between 50-130 (average 86, s: 29) for 10(6) mononuclear plated cells. A constant reactivation of fetal hemoglobin was found (from 1.4% to 11%, mean value 5.8%, s:3.07), but was lower than previously described, mainly because of the highly selective purification of Hb. This reactivation of fetal hemoglobin was not dependent upon the concentration of erythropoietin (from 1 U/ml to 6 U/ml) nor on the purity of the erythropoietin preparations (from 6 U/mg of protein to 70 000U/mg of protein). In addition, the same subject exhibited a constant proportion of Hb F synthesized in culture over a period of time up to 6 months. A positive correlation exists between the proportion of Hb F in culture and that of F cells present in the blood, with the exception of two subjects. Such findings suggest that Hb F in culture is a characteristic of each individual and that this reactivation often represents an amplification of the Hb F synthesis in vivo.

Adult↗

Difficulties in precise quantitation of CD4+ T lymphocytes for clinical trials: a review.

Maintenance of CD4+ T helper lymphocyte counts has been used as a surrogate marker of efficacy for drugs in the treatment of AIDS. In a multicenter clinical trial, subtle improvement of CD4+ T cell counts may be masked and misinterpreted if care is not paid to likely sources that can contribute to the variability of measurement of CD4+ T lymphocytes. This review addresses major areas that can contribute to the variability of measurement of CD4+ T lymphocytes, with emphasis on applications to multicenter clinical trials, and proposes areas of improvement that may not be well recognized by the medical community. Whereas there are excellent guidelines for immunophenotyping, equal attention is needed in hematologic enumeration of WBC and absolute lymphocytes. In particular, allowing the margin of error acceptable to blood cell standards for HIV-infected specimens is unsatisfactory. Special attention should also be given to the stability of lymphocytes in the anticoagulant during storage, the lysing method, the quality assurance programs as well as intrasubject fluctuations which may be derived from exercise, medications and diurnal variations. Awareness of these contributing factors by physicians and technical analysts will expedite the discovery of potential therapy in the treatment of AIDS. For a multicenter clinical trial, it is advisable to select a centralized laboratory adopting a uniform protocol with regard to sample preparation and handling, using more stringent quality controls for hematologic analysers, calibration of instruments and immunophenotyping. Pending a true reference standard that can monitor the variation of the entire analytical procedure, we anticipate that future interlaboratory quality assurance programs will include absolute T lymphocyte count, an important parameter for assessing the accuracy and consistency of CD4+ T helper cell counts generated from a laboratory.

Acquired Immunodeficiency Syndrome↗

Lipid-gramicidin interactions using two-dimensional Fourier-transform electron spin resonance.

The application of two-dimensional Fourier-transform electron-spin-resonance (2D-FT-ESR) to the study of lipid/gramicidin A (GA) interactions is reported. It is shown that 2D-FT-ESR spectra provide substantially enhanced spectral resolution to changes in the dynamics and ordering of the bulk lipids (as compared with cw-ESR spectra), that result from addition of GA to membrane vesicles of dipalmitoylphosphatidylcholine (DPPC) in excess water containing 16-PC as the lipid spin label. The agreement between the theory of Lee, Budil, and Freed and experimental results is very good in the liquid crystalline phase. Both the rotational and translational diffusion rates of the bulk lipid are substantially decreased by addition of GA, whereas the ordering is only slightly increased, for a 1:5 ratio of GA to lipid. The slowing effect on the diffusive rates of adding GA in the gel phase is less pronounced. It is suggested that the spectral fits in this phase would be improved with a more detailed dynamic model. No significant evidence is found in the 2D-FT-ESR spectra for a second immobilized component upon addition of GA, which is in contrast to cw-ESR. It is shown from simulations of the observed 2D-FT-ESR spectra that the additional component seen in cw-ESR spectra, and usually attributed to "immobilized" lipid, is inconsistent with its being characterized by increased ordering, according to a model proposed by Ge and Freed, but it would be consistent with the more conventional model of a significantly reduced diffusional rate. This is because the 2D-FT-ESR spectra exhibit a selectivity, favoring components with longer homogeneous relaxation times, T2. The homogeneous linewidths of the 2D-FT-ESR autopeaks appear to broaden as a function of mixing time. This apparent broadening is very likely due to the process of cooperative order director fluctuations (ODF) of the lipids in the vesicle. This real-time observation of ODF is distinct from, but appears in reasonable agreement with, NMR results. It is found that addition of GA to give the 1:5 ratio has only a small effect on the ODF, but there is a significant temperature dependence.

1,2-Dipalmitoylphosphatidylcholine↗

Survival of fiber cells and fiber-cell messenger RNA in lens of rats maintained on a 50% galactose diet for 45 days.

Previous work from this laboratory has shown that in cataractous lens from rats fed a 50% galactose diet up to 32 days, synthesis of crystallin mRNAs was reduced while synthesis of mRNAs for the non-crystallin proteins appeared to be maintained at equivalent or higher levels than found in the controls. In this study, we find that the population of mRNA from the 45-day cataractous lens included all of the crystallin mRNAs and substantial amounts of mRNAs for the non-crystallin proteins, in particular those proteins of molecular weights ranging from 45,000 to 92,000, and pIs from 5.5 to 7.0. At the 45-day cataractous stage, the observed mRNA products totaled between 100 and 120, while for the control they numbered between 40 and 50. In addition, hybrid-select measurements with a lambda gt11 MP26 clone established that MP26 mRNA persisted in the fiber cells of 11-, 20-, 32- and 45-day galactosemic lens. The data, therefore, suggest that continuous exposure of the lens to galactose apparently leads to significant fluctuations in mRNA synthesis and survival. Indirect immunofluorescence (with a monospecific polyclonal rabbit anti-MP26 antibody) and light-microscopy studies demonstrated that although the cortical fiber cells were swollen and structurally disoriented, they retained their nuclei, while the enucleated fiber cells were absent. The microscopy data also suggest that differentiation of the epithelial cells to fiber cells continued in the cataractous lens. Fiber-cell migration was backward as compared with the control, and the surviving cells were localized within the cortex and appeared to be surrounded by damaged cells or cell debris. It is suggested that persistent fiber-cell survival, and continued synthesis of various classes of mRNA by the nucleated cells in the cataractous lens could explain why reversal of cataracts results in recovery in both cell morphology and transparency in the non-nuclear portion of the lens.

Animals↗

Single sodium channels from rat brain incorporated into planar lipid bilayer membranes.

A voltage- and time-dependent conductance for sodium ions is responsible for the generation of impulses in most nerve and muscle cells. Changes in the sodium conductance are produced by the opening and closing of many discrete transmembrane channels. We present here the first report of electrical recordings from voltage-dependent sodium channels incorporated into planar lipid bilayers. In bilayers with many channels, batrachotoxin (BTX) induced a steady-state sodium current that was blocked by saxitoxin (STX) at nanomolar concentrations. All channels appeared in the bilayer with their STX blocking sites facing the side of vesicle addition, allowing us to define that as the extracellular side. Current fluctuations due to the opening and closing of single BTX-activated sodium channels were voltage-dependent (unit conductance, 30 pS in 0.5 M NaCl): the channels closed at large hyperpolarizing potentials. Slower fluctuations of the same amplitude, due to the blocking and unblocking of individual channels, were seen after addition of STX. Block of the sodium channels by STX was voltage-dependent, with hyperpolarizing potentials favouring block. The voltage-dependent gating, ionic selectivity and neurotoxin sensitivity suggest that these are the channels that normally underlie the sodium conductance change during the nerve impulse.

Animals↗

[Computer-assisted analysis of intrapartum cardiotocodynagraphs].

OBJECTIVE: To develop a numerical index by quantifying characteristic cardiotocography parameters in order to determine the intrauterine state of the fetus sub partu with sufficient accuracy to improve the diagnostic potential of cardiotocography. This score is then computerized for offline and online analysis. METHODS: The last 120 minutes of 406 directly recorded intrapartal cardiotocograms (CTG) were evaluated with a magnifying glass on the basis of conventional criteria. The mean basal frequency, the amplitude and the oscillation frequency of each individual baseline minute, the decelerations with depth, duration and type classification as well as the accelerations were determined. The Apgar score and the measurements of blood gases in the umbilical arterial and venous blood served as outcome parameters. The actual pH in the umbilical artery (UA) was the key variable. The newly developed CTG score was converted into a complex programming language after meticulous statistical testing and prepared for offline and online use. RESULTS: A score which is based on the CTG characteristics basal frequency level, baseline fluctuation and total decelerations area was developed on the basis of about 40 000 baseline minutes and more than 8 000 analysed decelerations from 406 fetuses which were all vaginal deliveries with a rate of acidosis (pH,UA < 7.100) of 9.8 % (deliberate selection). This score correlates highly significantly (r = -0.5752) with the actual umbilical arterial pH (p < 0.001). The correlation with the Apgar score (1 min) is r = -0.398, p < 0.001. The positive likelihood ratio (score 9) is 11.0 (95 % confidence interval 7.4-16.5) indicating that the test is very reliable. The score could be prepared for offline analysis of electronically registered CTGs with the assistance of a mathematician, so that the obstetrician's "eye work" can be dispensed with entirely. This program written in "C" also enables online evaluation of fetal heart rate patterns over time and a representation of the output parameters with acoustic and optical warning display options appropriate for the delivery room. CONCLUSIONS: Quantitative registration of fetal heart rate phenomena during delivery can be accomplished successfully by means of a score. The score correlates highly significantly with the actual pH value (UA) and the Apgar score (1 min). It is suitable both for offline and online analysis of intrapartal CTGs, and offers the prospect of quantitative fetal online monitoring.

Apgar Score↗

Cell-cycle-specific activity of cyclic nucleotide phosphodiesterase in Physarum polycephalum.

The cell-cycle-related activities of the cAMP- and cGMP-dependent phosphodiesterases of Physarum polycephalum were assayed. The activities of plasmodial homogenate and of selected subcellular fractions were measured. The results suggested the presence of both cAMP- and cGMP-dependent phosphodiesterase in the isolated nuclei of P. polycephalum. In addition, they reveal that the cAMP- and cGMP-dependent phosphodiesterase activities of the subcellular fractions fluctuate throughout the cell cycle. The whole-cell homogenates exhibit no cell-cycle-related changes in the presence of 5 X 10(-4) M cGMP. Kinetic data suggest the presence of multiple phosphodiesterase activities in the homogenate and its particulate fractions for the cGMP-dependent enzyme. Multiple cAMP activities are also suggested for the particulate fractions. The Km values indicate that the substrate affinities of the phosphodiesterases from P. polycephalum are similar to those found previously in mammalian systems.

3',5'-Cyclic-AMP Phosphodiesterases↗

Fluctuating asymmetry: an epigenetic measure of stress.

(1) Fluctuating asymmetry (FA) is a useful trait for monitoring stress in the laboratory and in natural environments. (2) Both genomic and environmental changes can increase FA which represents a deterioration in developmental homeostasis apparent in adult morphology. Genetic perturbations include intense directional selection and certain specific genes. Environmental perturbations include temperature extremes in particular, protein deprivation, audiogenic stress, and exposure to pollutants. (3) There is a negative association between FA and heterozygosity in a range of taxa especially fish, a result consistent with FA being a measure of fitness. (4) Scattered reports on non-experimental populations are consistent with experiments under controlled laboratory conditions. FA tends to increase as habitats become ecologically marginal; this includes exposure to environmental toxicants. (5) In our own species, FA of an increasing range of traits has been related to both environmental and genomic stress. (6) Domestication increases FA of the strength of homologous long bones of vertebrate species due to a relaxation of natural selection. (7) FA levels are paralleled by the incidence of skeletal abnormalities in stressful environments. (8) Increased FA is a reflection of poorer developmental homeostasis at the molecular, chromosomal and epigenetic levels.

Animals↗

Evolution of repeated DNA sequences by unequal crossover.

It is often supposed that highly repetitious DNA's arise only as a result of unusual mechanisms or in response to selective pressure. My arguments and simulations suggest, by contrast, that a pattern of tandem repeats is the natural state of DNA whose sequence is not maintained by selection. The simulations show that periodicities can develop readily from nonreptitious DNA as a result of the random accumulation of random mutations and random homology-dependent unequal crossovers. The lengths of these periodicities, and the patterns of subrepeats within them, would fluctuate in evolution, with the probability of a given pattern being dependent on the unknown exact nature of the crossover mechanism. Qualitatively, then, unequal crossover provides a reasonable and uncontrived explanation for the prevalence of highly repeated sequences in DNA and for the patterns of periodicity they evince.

Animals↗

Accuracy of noninvasive core temperature measurement in acutely ill adults: the state of the science.

Accurate temperature measurement is critical to the assessment and management of temperature fluctuation in the acutely ill adult. Unfortunately, an accurate, noninvasive method to measure core temperature has yet to be established, and current instruments produce a wide range of temperatures for any given patient. This article provides an integrative review of studies comparing selected invasive and noninvasive temperature measurement methods in acutely ill, hospitalized adult patients. Medline and CINAHL databases were searched to locate published studies on temperature measurement in the adult hospitalized patient. A partial list of primary search terms included core temperature measurement, oral temperature measurement, temporal artery thermometry, and tympanic thermometers. Studies that were data based and included comparison of a tympanic, temporal artery, and/or oral noninvasive temperature measurement to a pulmonary artery or esophageal invasive core measurement in an adult population were included in the analysis. The search method produced 223 publications and abstracts for initial review; 23 (10%) met the inclusion criteria. The only study evaluating the use of temporal artery thermometry in the adult population found the instrument to be unreliable. Results also indicate that high-quality evidence supporting the accuracy of tympanic thermometry, the preferred instrument for noninvasive core temperature measurement in many acute care settings, is lacking, and in fact, the most recent high-quality studies evaluating the accuracy of this instrument fail to show support for its use. Evidence does, however, support the use of oral thermometry as an accurate means of temperature assessment in the adult, acutely ill population.

Acute Disease↗