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PubMed2004

Measuring carotid stenosis on contrast-enhanced magnetic resonance angiography: diagnostic performance and reproducibility of 3 different methods.

BACKGROUND AND PURPOSE: The aim of this study was to compare diagnostic performance and reproducibility of 3 different methods of quantifying stenosis on contrast-enhanced magnetic resonance angiography (CEMRA), with intra-arterial digital subtraction angiography (DSA) as the reference standard. METHODS: 167 symptomatic patients scheduled for DSA, after screening Doppler ultrasound, were prospectively recruited to undergo CEMRA. Severity of stenosis was measured according to the North American Symptomatic Trial Collaborators (NASCET), European Carotid Surgery Trial (ECST), and the common carotid (CC) methods. Measurements for each method were made for 284 vessels (142 included patients) on both CEMRA and DSA in a blinded and randomized manner by 3 independent attending neuroradiologists. RESULTS: Significant differences in prevalence of severe stenosis were seen with the 3 methods on both DSA and CEMRA, with ECST yielding the least and NASCET the most cases of severe stenosis. Overall, all 3 methods performed similarly well in terms of intermodality correlation and agreement. No significant differences in interobserver agreement were found on either modality. With CEMRA, however, we found a significantly lower sensitivity for detection of severe stenosis with ECST (79.8%) compared with NASCET (93.0%), with DSA as reference standard. CONCLUSIONS: Uniformity of carotid stenosis measurement methods is desirable because patient management may otherwise differ substantially. All 3 methods are adequate for use with DSA. With CEMRA, however, this study supports use of the NASCET method because of improved sensitivity for detecting severe stenosis.

Adult↗
PubMed1993

Determination of serum cholesterol by stable isotope dilution method using discharge-assisted thermospray liquid chromatography/mass spectrometry.

A discharge-assisted thermospray (plasmaspray) liquid chromatography/mass spectrometric method for the determination of total serum cholesterol is described. The method incorporates stable isotope dilution using (3,4-13C)cholesterol as an internal standard. Liquid chromatographic separation is performed using methanol as a flow solvent and effluents are directly introduced to the mass spectrometer. [MH-H2O]+ ions are monitored during liquid chromatography/mass spectrometry using the selected ion monitoring method. Satisfactory agreement between the analytical result and the certified value of the National Institute of Standards and Technology (formerly National Bureau of Standards) standard reference material serum is obtained with a relative standard deviation of 0.6%.

Cholesterol↗
PubMed1999

Magnetic resonance imaging and audiologic assessment of middle ear effusions in patients with nasopharyngeal carcinoma before radiation therapy.

OBJECTIVE: The aim of this study was to assess the performance of clinical methods, viz. otoscopy, pure-tone audiometry, and tympanometry in diagnosing middle ear effusions (MEEs) using magnetic resonance imaging as a reference standard. STUDY DESIGN: A retrospective study of 46 patients with newly diagnosed nasopharyngeal carcinoma was performed comparing clinical evaluation and audiometry results with magnetic resonance imaging findings obtained before radiation therapy. RESULTS: Twenty-two (25%) of the temporal bones imaged had both MEE and mastoid effusions, 24 (27%) had only middle ear fluid, and 29 (33%) had mastoid fluid alone. The sensitivity for tympanometry, audiometry, and otoscopy in detecting fluid in the middle ear was 96%, 92%, and 80%, respectively. Although tympanometry was most sensitive in diagnosing MEE, there was no statistically significant difference when comparing the overall accuracy of pure-tone audiometry air-bone gap and tympanometry (p = 0.7, chi-square test). Flat curve tympanograms (type B) only achieved a sensitivity of 45% but were of high specificity (92%). Forty-nine percent with negative pressure tympanograms (mean air pressures > -100 daPa) had no MEE. CONCLUSIONS: Using magnetic resonance imaging as a reference standard, tympanometry is the most sensitive audiologic test in detecting the presence of MEE. The overall accuracy of tympanometry, pure-tone audiometry air-bone gap, and otologic examination was, however, not significantly different.

Acoustic Impedance Tests↗
PubMed1997

Reference Techniques for Left Ventricular Volume Measurement by Three-Dimensional Echocardiography: Determination of Precision, Accuracy, and Feasibility.

The use of multiple in vitro reference methods to validate three-dimensional (3-D) echocardiographic techniques makes comparison difficult. In an attempt to establish a reference standard, we studied precision, accuracy, and feasibility of a true left ventricular (LV) volume measurement in six dog heart specimens using three techniques, called fluid, sheath, and cast. LV volumes ranged from 30 to 105 mL. Intraobserver variability was minimal in all combinations (1.26% to 2.8%) with a statistically insignificant tendency to higher values in the cast method. The cast method, however, exhibited significantly higher interobserver variability (5.78%) as compared to that ranging from 1.47% to 1.59% in the remaining two techniques. Regression analysis demonstrated high correlations among the three techniques assessed by 95% confidence limits and correlation coefficient (R(2) > 0.98, P < 0.01). Mean differences among the techniques (0.12 to 1.08 mL) were not significant. The fluid technique was easy to perform. The sheath technique required some practice. The cast method was sensitive to accurate preparation of a gelatin mixture. We conclude that the fluid and sheath techniques are precise, accurate, and feasible. We recommend their use as reference standards in laboratory LV volume measurement. Validation 3-D echocardiographic studies using either of these two techniques will be comparable. Although the accuracy of the cast technique is excellent, its lower precision makes it a second choice. It could be used in cases where an LV cavity cast is required and higher interobserver variability is acceptable.

Journal Article↗
PubMed2003

Comparison of the Directigen flu A+B test, the QuickVue influenza test, and clinical case definition to viral culture and reverse transcription-PCR for rapid diagnosis of influenza virus infection.

The diagnostic performances of the clinical case definition of influenza virus infection based on the combination of fever and cough and of two rapid influenza diagnostic tests, the Directigen Flu A+B test (Directigen; BD Diagnostic Systems, Sparks, Md.) and the QuickVue influenza test (QuickVue; Quidel, San Diego, Calif.), were compared to those of viral culture and an in-house reverse transcription (RT)-PCR during the 2000-2001 flu season. Two hundred consecutive nasopharyngeal aspirates were analyzed from 192 patients, including 122 adults and 70 children. Viral culture identified influenza virus A in 16 samples and influenza virus B in 55 samples, whereas RT-PCR identified influenza virus A in 21 samples and influenza virus B in 64 samples. When RT-PCR was used as the reference standard, the likelihood ratios for a positive test were 40.0 for Directigen, 8.6 for QuickVue, and 1.4 for the combination of fever and cough, whereas the likelihood ratios for a negative test were 0.22, 0.16, and 0.48, respectively. Our study suggests that (i). the poor specificity (35 to 58%) and the poor positive predictive value (41 to 60%) of the clinical case definition of influenza preclude its use for prediction of influenza virus infections during epidemics, especially when infection control decision making in the hospital setting is considered; (ii). Directigen has a higher diagnostic yield than QuickVue but is associated with a larger number of invalid results; (iii). the sensitivities of the rapid diagnostic tests are significantly lower with samples from adults than with samples from children, with the rates of false-negative results reaching up to 29%; and (iv). RT-PCR detects more cases of influenza than viral culture, and this greater accuracy makes it a more useful reference standard.

Base Sequence↗
PubMed1995

Comparison of 99m technetium hexamethylpropylene-amine oxime labelled leucocyte with 111-indium tropolonate labelled granulocyte scanning and ultrasound in the diagnosis of intra-abdominal abscess.

Fifty patients with suspected intra-abdominal abscess were investigated prospectively with ultrasound and with 99mTc-hexamethylpropylene-amine oxime (HMPAO) isotope labelled mixed leucocytes, using 111-In tropolonate granulocyte scanning as the reference standard. Twenty five patients had inflammatory bowel disease (three were postoperative): 21 of these had Crohn's disease and four had ulcerative colitis. The remainder comprised nine with postoperative fever and 16 with fever and abdominal pain. An abscess was diagnosed when focal activity on serial 111-In tropolonate and 99m-Tc-HMPOA images at one, three, and 24 hours resulted in activity at least equal to liver activity at 24 hours. Thirteen abscesses were diagnosed using each type of white cell scanning, resulting in 100% sensitivity for 99m-Tc-HMPAO compared with 111-In tropolonate. Bowel inflammation was easily distinguished from abscess on serial images. Eight of these 13 abscesses were detected by ultrasound. Altogether 17 abscesses were found. Ultrasound detected 12, including four liver abscesses which were not purulent and had not been detected by white cell scanning. Ultrasound had a sensitivity of 71% (12 of 17) and a specificity of 87% (33 of 38) using all confirmed abscesses as the reference standard. White cell scanning showed a sensitivity of 76% (13 of 17: as a result of the four non-purulent liver abscesses) and a specificity of 100%. 99m-Tc-HMPAO scanning is as accurate as 111-In tropolonate scanning, and has several advantages including simplicity, availability, superior image quality, and reduced radiation dose. Both methods are more sensitive and specific than ultrasound for intra-abdominal abscess detection but ultrasound is advisable if a neutrophil infiltrate is not suspected.

Abdominal Abscess↗
PubMed1997

Comparison of echocardiography with magnetic resonance imaging in the assessment of the athlete's heart.

AIM: The purpose of the study was to compare the accuracy of M-mode echocardiography and two different two-dimensional echocardiographic approaches in the assessment of left ventricular mass and volumes in endurance-trained and strength-trained athletes, using magnetic resonance imaging as reference standard. METHODS AND RESULTS: We studied 19 athletes and 10 untrained control subjects, M-mode and two-dimensional echocardiography were compared to magnetic resonance imaging. M-mode echocardiographic left ventricular mass was calculated using the Penn cube convention. Two-dimensional echocardiographic left ventricular mass was calculated using (1) the area-length method as proposed by the American Society of Echocardiography (ASE) and (2) as proposed by Reichek. The best correlation between magnetic resonance imaging and echocardiographic left ventricular mass and volumes was observed with the ASE two-dimensional echocardiographic method. The agreement between them (-3.4 +/- 7.6 g and 18.5 +/- 19.5 ml) was better than between Reichek two-dimensional echocardiography and magnetic resonance imaging (-39.4 +/- 15.4-g and 52.8 +/- 21.7 ml), and demonstrated less random difference than M-mode echocardiography and magnetic resonance imaging (3.2 +/- 21.1 g resp. 15.1 +/- 30.0 ml). CONCLUSION: We conclude that the ASE two-dimensional echocardiographic approach, when using magnetic resonance imaging as a reference standard, was the most accurate estimator of left ventricular mass and volumes in both controls and athletes.

Adult↗
PubMed2003

Isomer specific synthesis using the Suzuki-coupling. Polychlorinated terphenyls as standards for environmental analysis.

Defined polychlorinated terphenyl (PCT) single congeners as reference standards are the prerequisite for the development of analytical methods for their determination and quantification in the environment. The selective synthesis of PCTs for environmental analytical purposes by application of the Suzuki-coupling reaction is described. Under easily modified standard reaction conditions of this coupling process the PCTs can be obtained by reaction of benzeneboronic acids with dibromobenzenes mostly in good yields, as described by the synthesis of following PCT congeners: p-PCT (3,3("),5,5(")-tetrachloro-, 2,2("),4,4(")-tetrachloro-, 2('),3,3("),5,5(")-pentachloro-); m-PCT (3,3("),5,5(")-tetrachloro-) and o-PCT (3,3("),5,5(")-tetrachloro-). The terphenyl congeners were characterized by NMR (1H, 13C)- and FT-IR-spectroscopy. Their purity was checked by GC/MS analysis. The experimental and quantum-chemically calculated FT-IR-spectra were compared and it was shown, that the determination of the chlorine substitution pattern in the terphenyl congeners by their typical absorption spectra is possible.

Environmental Monitoring↗
PubMedDate not supplied

[Hemophilic arthropathy: echography and radiology].

Our experience is reported with the combined use of radiology and US in the study of 210 joints of hemophilic patients. The study was carried out considering that in hemophilia the classification of the grades of disease generally relies upon X-ray findings which, although reliable in the advanced stages of the disease, appear inadequate in the early stages. In fact, synovial hypertrophy, cartilage erosions and initial subchondral cysts are most often missed on X-ray films. In the examined cases, US was employed to evaluate: 1) the degree of synovial hypertrophy, 2) the status of the explorable cartilage, 3) the presence of effusions and 4) the status of bone linings--whenever erosions, even of minimal extent, were suspected, X-rays were always performed and the results employed as the reference standard. The examined joints did not exhibit the same grade of involvement: the knee, elbow and ankle had advanced arthropathy in 85% of cases, corresponding to > or = 7 according to Pettersson score. On the contrary, the shoulder and hip were found to be equally involved either by initial (Pettersson score: 0-6) or by advanced arthropathy (Pettersson score: > or = 7). Moreover, in nearly 10% of the cases, hemarthrosis was found which showed no correlation with the grade of joint involvement. Our results indicate that: 1) US appears very useful in the early stages of the disease when the X-ray picture is negative or poorly significant. The demonstration of early alterations is useful mainly in those cases in whom synoviectomy is considered (for prevention); the latter is useful only if performed before cartilage erosion appear; 2) US appears equally useful in hemarthrosis cases, especially in those of limited extent in which the clinical therapeutic management may be difficult; 3) US appears unnecessary in the cases of advanced arthropathy in which X-rays serve as the reference standard.

Arthrography↗
PubMed2002

Utility of hematuria testing in patients with suspected renal colic: correlation with unenhanced helical CT results.

OBJECTIVES: To determine the utility of hematuria testing in a large series of patients with suspected renal colic using unenhanced helical computed tomography (CT) as the reference standard. METHODS: A retrospective review of the CT reports of all patients who underwent unenhanced helical CT for suspected renal colic at one institution during a 3.5-year period and who also underwent a formal microscopic urinalysis within 24 hours of the CT study was conducted. The sensitivity, specificity, positive predictive value, and negative predictive value of the presence of any blood on the urinalysis for renal colic were calculated. RESULTS: Urolithiasis was present in 587 (62%) of the 950 patients, and 363 patients had negative examinations for renal colic, including 69 with significant alternative diagnoses in the latter group. Of the urinalyses, 492 were true-positive, 174 were true-negative, 189 were false-positive, and 95 were false-negative, yielding a sensitivity, specificity, positive predictive value, and negative predictive value of 84%, 48%, 72%, and 65%, respectively. Forty-six percent of the urinalysis results were negative for blood in the subset of patients with significant alternative diagnoses. CONCLUSIONS: The sensitivity of hematuria on microscopic urinalysis for renal colic using unenhanced CT as the reference standard was 84%, and the specificity and negative predictive value was low. The presence or absence of blood on urinalysis cannot be used to reliably determine which patients actually have ureteral stones.

Colic↗
PubMed2005

Anterior shoulder instability: accuracy of MR arthrography in the classification of anteroinferior labroligamentous injuries.

PURPOSE: To retrospectively evaluate the accuracy of magnetic resonance (MR) arthrography in the classification of anteroinferior labroligamentous injuries by using arthroscopy as the reference standard. MATERIALS AND METHODS: Ethical committee approval and informed consent were obtained. MR arthrograms obtained in 205 patients, including a study group of 104 patients (74 male and 30 female; mean age, 28.2 years) with arthroscopically proved labroligamentous injuries and a control group of 101 patients (65 male and 36 female; mean age, 31.4 years) with intact labroligamentous complex, were reviewed in random order. MR arthrograms were analyzed for the presence and type (Bankart, anterior labral periosteal sleeve avulsion [ALPSA], Perthes, glenolabral articular disruption [GLAD], or nonclassifiable lesion) of labroligamentous injuries by two radiologists in consensus. Results were compared with arthroscopic findings. Sensitivity, specificity, accuracy, and corresponding 95% confidence intervals for the detection and classification of anteroinferior labroligamentous lesions with MR arthrography were calculated. RESULTS: At arthroscopy, 104 anteroinferior labroligamentous lesions were diagnosed, including 44 Bankart lesions, 22 ALPSA lesions, 12 Perthes lesions, and three GLAD lesions. Twenty-three labral lesions were nonclassifiable at arthroscopy, all of which occurred after a history of chronic instability. Nineteen (83%) of these 23 lesions were also nonclassifiable at MR arthrography. With arthroscopy used as the reference standard, labroligamentous lesions were detected and correctly classified at MR arthrography with sensitivities of 88% and 77%, specificities of 91% and 91%, and accuracies of 89% and 84%, respectively. Bankart, ALPSA, and Perthes lesions were correctly classified in 80%, 77%, and 50% of cases, respectively. The three GLAD lesions were all correctly assessed. CONCLUSION: MR arthrography is accurate in enabling classification of acute and chronic anteroinferior labroligamentous injuries, although correct interpretation of Perthes lesions remains difficult.

Adolescent↗
PubMed2004

Suspected acute pulmonary embolism: evaluation with multi-detector row CT versus digital subtraction pulmonary arteriography.

PURPOSE: To determine diagnostic accuracy of four-channel multi-detector row computed tomography (CT) in emergency room and inpatient populations suspected of having acute pulmonary embolism (PE) who prospectively underwent both CT and pulmonary arteriography (PA). MATERIALS AND METHODS: Patients referred for PA to assess suspected PE were eligible. Institutional review board approval and written informed consent were obtained. All patients underwent CT and PA within a 48-hour period. For CT, 4 x 2.5-mm collimation was used. Three readers independently evaluated each study for PE presence. PE status, vessel level, and lobar location were determined by means of majority rule, and interobserver agreement (kappa) was calculated for PE status, as assessed with each modality. Sensitivity and specificity of CT were calculated by using PA as the reference standard. Two radiologists later reviewed false-positive CT studies. RESULTS: The study group comprised 93 patients (median age, 56 years; range, 19-88 years). Sensitivity, specificity, and accuracy of CT were 100%, 89%, and 91%, respectively. kappa values were 0.71 and 0.83 for CT and PA, respectively, and were not significantly different between modalities. At PA, 18 patients (19%) had PE at 50 vessel levels (five main and/or interlobar, 24 segmental, and 21 subsegmental), 17 (94%) of which had PE at multiple sites. At CT, 26 patients (28%) had PE at 71 vessel levels (24 main and/or interlobar, 33 segmental, and 14 subsegmental). Twenty patients (77%) had PE at multiple sites. Review of eight false-positive CT studies showed an appearance highly suggestive of acute PE in three patients, chronic PE in one, and no PE in three; one study was inconclusive. CT better demonstrated large-level vessel involvement (P < .01), while PA better demonstrated small-level vessel involvement (P < .01). CONCLUSION: Multi-detector row CT has an accuracy of 91% in the depiction of suspected acute PE when conventional PA is used as the reference standard.

Acute Disease↗
PubMed2006

Upper-extremity venography: CO2 versus iodinated contrast material.

PURPOSE: To determine prospectively the diagnostic performance of CO(2) venography, by using conventional venography with iodinated contrast material as the reference standard, for the preoperative evaluation of upper-limb and central veins before creation of fistulas for hemodialysis access. MATERIALS AND METHODS: The study was approved by the institutional review board, and informed consent was obtained from all patients. Twenty-two patients underwent comparative CO(2) and conventional venography of upper-extremity and central veins. Two independent observers evaluated the opacification of the veins and grade of stenosis, if present. Interobserver agreements were estimated with the Cohen kappa coefficient. Calculations of sensitivity, specificity, and accuracy were used for intertechnique observations. RESULTS: For CO(2) venography, global interobserver agreement was good, with a kappa value of 0.90 (range, 0.71-1.00; 95% confidence interval: 0.84, 0.95). A kappa value of 0.96 (range, 0.86-1.00; 95% confidence interval: 0.93, 0.99) was calculated for global interobserver agreement for conventional venography. The sensitivity, specificity, and accuracy of CO(2) venography for all vein segments were 97%, 85%, and 95%, respectively. CONCLUSION: CO(2) venography had a sensitivity of 97% and a specificity of 85% in the assessment of upper-limb and central vein patency and stenosis, with conventional venography used as the reference standard.

Aged↗
PubMed2000

MRA versus digital subtraction angiography in acute subarachnoid haemorrhage: a blinded multireader study of prospectively recruited patients.

We performed a blinded multireader study comparing MR angiography (MRA) with digital subtraction angiography (DSA) in 34 prospectively recruited patients who presented with acute subarachnoid haemorrhage (SAH). Two observers independently reviewed the MRA and DSA studies some months after clinical presentation. Presence of an aneurysm was rated on a 4-point confidence scale. Cases in which the initial interpretation of the observers varied were jointly reviewed to reach a consensus opinion. DSA was deliberately chosen not to represent the reference standard and the clinical course and surgical findings were used to explain significant differences between the consensus readings of MRA and DSA. Diagnostic confidence and interobserver agreement were, overall, higher on DSA than on MRA studies (kappa DSA = 0.64 versus kappa MRA = 0.52 with 95% CI for delta = kappa DSA-kappa MRA [-0.06, 0.31]). With both methods, discrepancies between observers were due to aneurysms overlooked rather than false-positive readings by one observer. Diagnostic accuracy therefore improved when the readings of the two observers were combined, particularly for MRA. Intermethod agreement was only fair and similar for both readers (kappa reader 1 = 0.37 versus kappa reader 2 = 0.32 with 95% CI for delta = kappa reader 1-kappa reader 2 [-0.02, 0.11]). Both interobserver and intermethod agreements improved when the data were analysed on a per-study (positive or negative study) rather than on a per-aneurysm basis. Differences in the consensus reading were due to five aneurysms (four single and one multiple) detected only with MRA and five (two single and three multiple) detected only with DSA. MRA and DSA should be regarded as complementary in the investigation of patients with acute SAH. DSA can no longer be regarded as the reference standard.

Adult↗
PubMed2004

Topological measurement of an A-tract bend angle: effect of magnesium.

Sequences of four to six adenine residues, termed A-tracts, have been shown to produce curvature in the DNA double helix. A-tracts have been used extensively as reference standards to quantify bending induced by other sequences as well as by DNA binding proteins when they bind to their sites. However, the ability of an A-tract to serve as such a standard is hampered by the wide variation of values reported for the amount of bend conferred by an A-tract. One experimental condition that differs in these studies is the presence of divalent cation. To evaluate this effect, a new application of a topological method, termed rotational variant analysis, is used here to measure for the first time the effect of the presence of magnesium ion on the bend angle conferred by an A-tract. This method, which has the unique ability to measure a bend angle in the presence or absence of magnesium ion, demonstrates that magnesium ion markedly increases the bend angle. For example, when measured in a commonly used gel electrophoretic buffer, the bend angle conferred by a tract of six adenine residues increases from about 7 degrees in the absence of magnesium ion to 19 degrees in the presence of 3.9 mM magnesium ion. This quantitative demonstration of substantial magnesium ion dependence has several important implications. First, it explains discrepancies among bend values reported in various previous studies, particularly those employing gel electrophoretic versus other solution methods. In addition, these findings necessitate substantial revisions of the conclusions in a large number of studies that have used A-tract DNA as the bend angle reference standard in comparison measurements. Finally, any such future studies employing this comparison methodology will need to use the same sequence analyzed in the original measurements as well as replicate the original measurement conditions (e.g. ionic composition and temperature).

Adenine↗
PubMed1999

The head arterial glucose level is not the reference site for generation of the portal signal in conscious dogs.

Experiments were performed on twelve 42-h-fasted, conscious dogs to determine whether the head arterial glucose level is used as a reference standard for comparison with the portal glucose level in bringing about the stimulatory effect of portal glucose delivery on net hepatic glucose uptake (NHGU). Each experiment consisted of an 80-min equilibration, a 40-min control, and two 90-min test periods. After the control period, somatostatin was given along with insulin (7.2 pmol. kg(-1). min(-1); 3.5-fold increase) and glucagon (0.6 ng. kg(-1). min(-1); basal) intraportally. Glucose was infused intraportally (22.2 micromol. kg(-1). min(-1)) and peripherally as needed to double the hepatic glucose load. In one test period, glucose was infused into both vertebral and carotid arteries (HEAD(G); 22.2 +/- 0.8 micromol. kg(-1). min(-1)); in the other test period, saline was infused into the head arteries (HEAD(S)). One-half of the dogs received HEAD(G) first. When all dogs are considered, the blood arterial-portal glucose gradients (-0.52 +/- 0.07 vs. -0.49 +/- 0.03 mM) and the hepatic glucose loads (339 +/- 14 vs. 334 +/- 20 micromol. kg(-1). min(-1)) were similar in HEAD(G) and HEAD(S). NHGU was 24.1 +/- 3.8 and 25.1 +/- 4.6 micromol. kg(-1). min(-1), and nonhepatic glucose uptake was 46.1 +/- 4.2 and 48.8 +/- 7.0 micromol. kg(-1). min(-1) in HEAD(G) and HEAD(S), respectively. The head arterial glucose level is not the reference standard used for comparison with the portal glucose level in the generation of the portal signal.

Animals↗
PubMed2001

Apoptosis in the in vivo mammalian forebrain.

Apoptosis is a word originally introduced by Kerr, Wyllie, and colleagues for a cell death process they defined in terms of its ultrastructural appearance in nonneuronal cells from various tissues. There are very few studies providing detailed ultrastructural criteria for recognizing neuronal apoptosis in the in vivo mammalian brain. In the absence of such criteria, the Kerr/Wyllie description pertaining to nonneuronal cells has served as a reference standard. However, contemporary neurobiologists typically rely on cell culture models for studying neuronal apoptosis, and these models are rarely validated ultrastructurally; rather they are assumed to be appropriate models based on unvalidated biochemical tests for apoptosis. Relying on evidence generated in such cell culture models or on nonspecific cytochemical tests applied to brain tissue, many authors have recently suggested that an apoptotic mechanism may mediate neuronal death in a wide variety of human neurodegenerative diseases. Whether the cell death process in neurodegenerative diseases meets ultrastructural criteria for apoptosis has been given very little consideration. Recently, several methods have been described for triggering extensive apoptotic neurodegeneration in the developing in vivo mammalian brain. These methods include head trauma or treatment with several types of drugs (NMDA antagonists, GABAA agonists, or ethanol). We have performed an ultrastructural analysis of the neuronal cell death process triggered in the cerebral cortex and thalamus by these several methods and compared it with physiological cell death (PCD), a prototypic example of neuronal apoptosis that occurs naturally in the developing brain. Our findings, which are reviewed herein, demonstrate that the types and sequence of changes induced by each of the above methods are identical to those that characterize PCD. This confirms that each of these methods produces bona fide in vivo apoptotic neurodegeneration, and it signifies that our description of this neuronal apoptotic process, which differs in some respects from the Kerr/Wyllie description of nonneuronal apoptosis, can serve as a useful reference standard for recognizing the characteristic changes that in vivo neurons undergo when they are dying by an apoptotic mechanism.

Animals↗
PubMed1986

Intrauterine volume in pregnancy.

Intrauterine volume, a three-dimensional measure of growth, was evaluated in pregnancy. The ultrasonic method for measurement of volume was investigated for its accuracy and error potentials and then used to collect information on the growth of three volume components, - total intrauterine, intra-amniotic and placental volume, in the latter half of normal pregnancy. Against reference standards from the normal population, two other main groups, a non-selected and a pre-selected high-risk group, were studied, to test the hypothesis that a small intrauterine volume would predict the presence of a small-for-dates and possibly compromised baby. In previous times main interest in uterine volume had centered on its possible role in parturition. More recently ultrasound had been used to measure intrauterine volume in early pregnancy and a simple ultrasonic method of calculating total intrauterine volume had been used for diagnosing the small-for-dates fetus. The study showed that in a phantom model situation, a method based on serial parallel planimetric area measurements was significantly more accurate than a linear measurement method that assumed the uterine shape to be like a prolate ellipsoid. With the former method 93.3% of measurements were within +/- 5% of the true volume with a mean error of -0.43%. When the method was evaluated for its accuracy in women undergoing midtrimester termination or in women delivering near term, there was good correlation between ultrasonically and directly/indirectly measured intra-amniotic volume suggesting that the same level of accuracy could be expected in pregnancy as found in the phantom models. Intra- and interobserver variation was small. The PPA method was used for all measurements in pregnancy because of its superior accuracy. Data from 115 healthy women with no pregnancy complications were evaluated longitudinally to study normal growth and derive reference standards. Median and mean values for total intrauterine volume increased from around 1,000 ml at 20 weeks to 4,500 ml at 40 weeks. The standard deviation was large at any stage of pregnancy, also for intra-amniotic and placental volume. The rate of volume increase was near constant for total intrauterine and intra-amniotic volumes, except during the period 30-35 weeks, when a faster rise was observed. Placental volume growth decreased after 30 weeks. With growth of total volume following a largely linear trend, a tendency for ranking of volume levels was observed, but predictability of one measurement on the basis of earlier ones weakened with increasing separation of time points.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗