Ground-based assessment of the bias and long-term stability of fourteen limb and occultation ozone profile data records.

The ozone profile records of a large number of limb and occultation satellite instruments are widely used to address several key questions in ozone research. Further progress in some domains depends on a more detailed understanding of these data sets, especially of their long-term stability and their mutual consistency. To this end, we made a systematic assessment of fourteen limb and occultation sounders that, together, provide more than three decades of global ozone profile measurements. In particular, we considered the latest operational Level-2 records by SAGE II, SAGE III, HALOE, UARS MLS, Aura MLS, POAM II, POAM III, OSIRIS, SMR, GOMOS, MIPAS, SCIAMACHY, ACE-FTS and MAESTRO. Central to our work is a consistent and robust analysis of the comparisons against the ground-based ozonesonde and stratospheric ozone lidar networks. It allowed us to investigate, from the troposphere up to the stratopause, the following main aspects of satellite data quality: long-term stability, overall bias, and short-term variability, together with their dependence on geophysical parameters and profile representation. In addition, it permitted us to quantify the overall consistency between the ozone profilers. Generally, we found that between 20-40 km the satellite ozone measurement biases are smaller than ±5 %, the short-term variabilities are less than 5-12% and the drifts are at most ±5% decade-1 (or even ±3 % decade-1 for a few records). The agreement with ground-based data degrades somewhat towards the stratopause and especially towards the tropopause where natural variability and low ozone abundances impede a more precise analysis. In part of the stratosphere a few records deviate from the preceding general conclusions; we identified biases of 10% and more (POAM II and SCIAMACHY), markedly higher single-profile variability (SMR and SCIAMACHY), and significant long-term drifts (SCIAMACHY, OSIRIS, HALOE, and possibly GOMOS and SMR as well). Furthermore, we reflected on the repercussions of our findings for the construction, analysis and interpretation of merged data records. Most notably, the discrepancies between several recent ozone profile trend assessments can be mostly explained by instrumental drift. This clearly demonstrates the need for systematic comprehensive multi-instrument comparison analyses.

Rapid plasma virus and CD4+ T-cell turnover in HIV-1 infection: evidence for an only transient interruption by treatment.

OBJECTIVES: To analyse the short-term kinetics of viral plasma RNA and CD4+ T cells numbers in patients with different initial CD4+ T-cell counts treated with different antiretroviral regimens. METHODS: In 10 HIV-1 positive patients, in vivo kinetics of plasma HIV RNA and CD4+ T cells were studied during antiretroviral treatment. Lymphocyte subpopulation analysis, quantitative polymerase chain reaction (PCR), p24 antigen enzyme immunoassay (EIA) and beta 2-microglobulin EIA were performed at days 0, 3, 7, 10, 14, 21 and 28 of treatment. One additional patient served as a control. The resulting curves were fitted. Half-lives were calculated using the time constant T of decrease or increase [T1/2 = In(2) x T]. Calculations of virus and CD4+ T-cell turnover were multiplied by the total blood volume. RESULTS: Viral plasma RNA half-life ranged from 1.1 to 5.1 days, independent of prior or actual treatment and initial CD4+ T-cell count. The calculated peripheral blood viral plasma RNA turnover varied between 0.02 and 55.8 x 10(8) copies/ml/day and showed some negative correlation with initial CD4+ T-cell counts. CD4+ T-cell turnover estimates ranged from 0.01 to 7.5 x 10(8) cells/day. Most patients showed an immediate reincrease of virus load after the nadir. Changes in HIV p24 antigen paralleled HIV plasma RNA in p24 antigen-positive patients. beta 2-microglobulin decreased until day 7-15 in all but one case and rapidly reincreased to pretreatment values. CONCLUSIONS: The kinetics of virus and CD4+ T-cell turnover are uniformly rapid throughout a wide range of initial CD4+ T-cell counts. The magnitude of virus turnover varies considerably among individuals and appears to be inversely related to the initial CD4+ T-cell count. These data also argue for a rapid resumption of virus production and lymphocyte turnover during treatment.

Anchorage independent colony growth of fetal hamster lung epithelial cells after treatment with diepoxybutane.

To test the reliability of a new cell transformation assay, a cloned fetal Syrian hamster lung epithelial cell line (M3E3/C3) was used. The target cells originating from the respiratory tract were treated in vitro over a concentration range of 0-10(-5) M/l with diepoxybutane, cultured during the expression period of 28 or 35 days and then transferred into soft agar. Anchorage independent colony growth in soft agar occurs only if cells are transformed. Growth and number of colonies were taken as a score of the carcinogenic potential of the test substance. Under the conditions of this cell transformation assay it was possible to detect the carcinogenic potential of diepoxybutane unequivocally.

Differentiation between fresh and thawed meat by an enzyme profile test.

Exudates from fresh (stored at +4°C) and thawed pork and beef (frozen and stored below -20°C) was assayed by the rapid test kit API-ZYM(TM) to determine enzyme profiles. The test kit consists of 20 wells for different enzyme substrates. Of altogether 1040 results, only few reactions of the enzymes differed in their intensity between frozen and thawed pork or beef. Fresh pork showed a more intensive ß-galactosidase and N-acetyl-ß-glucosaminidase reaction while with fresh beef a more intensive reaction could only be detected for N-acetyl-ß-glucosaminidase. Only N-acetyl-ß-glucosaminidase showed significant differences between fresh and frozen meat in both species (α = 0·01). Considering the indistinct results of the test kit differentiation between frozen and thawed meat, the API-ZYM(TM) test kit is considered not suitable for distinguishing frozen from thawed pork or beef.

Evaluation of coronary flow reserve using myocardial contrast echocardiography in humans.

To evaluate the applicability of myocardial contrast echocardiography for the assessment of coronary blood flow reserve, 21 consecutive patients undergoing coronary angiography were studied. Only patients with a single left anterior descending lesion or normal coronary angiogram were included. Intracoronary injections of sonicated albumin were performed before and after the administration of intracoronary papaverine. Good quality studies at baseline and after the administration of papaverine were obtained in 14 of 21 patients. Ten patients had a significant (greater than 75%) single left anterior descending lesion and four had normal or insignificant lesions (70% or less stenosis) in the left anterior descending coronary artery. Time-intensity curves for the left anterior descending coronary artery region of interest were generated and then the peak contrast intensity (PCI), washout half-time (T1/2) and the area under the curve (AUC) were calculated. The post-papaverine increases in PCI and in the AUC, compared to baseline, were 55 +/- 22% and 102 +/- 14% in the four patients with 70% or less left anterior descending diameter stenosis serving as a control group and 3 +/- 25% and 40 +/- 10%, respectively, in the 10 patients with significant left anterior descending coronary artery disease (mean +/- 1 SD, P less than 0.01). In patients with normal coronary arteriography T1/2 increased after intracoronary injection of papaverine. In patients with severe lesions, either an increase or a decrease in T1/2 was observed. Significant left anterior descending coronary artery stenosis associated with impaired coronary blood flow reserve can be detected by failure of myocardial contrast echocardiographic parameters to increase after injection of papaverine. Mild and transient side effects were noted in three patients.

Intravenous contrast echocardiography with use of sonicated albumin in humans: systolic disappearance of left ventricular contrast after transpulmonary transmission.

The transmission of echocardiographic contrast medium and the cyclic changes in left ventricular videodensity during transpulmonary contrast echocardiography were investigated in nine adult volunteers with the use of intravenous injections of sonicated albumin (microbubble size 5.2 +/- 2.6 microns). Right and left ventricular and myocardial contrast were quantitated by videodensitometric analysis. The injections caused no symptoms, and no hemodynamic or electrocardiographic changes were observed. All injections resulted in right ventricular contrast. Mean peak right ventricular videodensity was 75 +/- 48 at end-diastole and 61 +/- 36 gray scale U/pixel at end-systole (p less than 0.05). Seventy-eight percent of injections resulted in left ventricular contrast with a mean peak videodensity of 21 +/- 33 gray scale U/pixel. Early systole was associated with a rapid decrease in left ventricular contrast intensity with near total disappearance of contrast by end-systole (from 23 +/- 33 and 17 +/- 23 U/pixel at end-diastole to 6 +/- 10 and 3 +/- 2 at end-systole at the left ventricular base and apex, respectively; p less than 0.05). None of the injections resulted in myocardial contrast enhancement by visual or quantitative analysis. Thus, left ventricular contrast echocardiography can be achieved after intravenous injections of sonicated albumin. Transpulmonary left ventricular contrast echocardiography is associated with near total disappearance of contrast during systole. This may be secondary to the destruction of microbubbles by the high left ventricular systolic pressure. These findings may help explain the limited success of this technique thus far for myocardial perfusion imaging.

Myocardial perfusion studies by contrast echocardiography.

Determination of regional myocardial blood flow may provide clinically valuable information about ischemia, risk area, and the effect of angioplastic, surgical, and pharmacologic interventions. Contrast echocardiography, with use of prepared microbubbles of 4 to 8 microns size, graphically demonstrates perfusion characteristics in the catheterization laboratory. Analysis and interpretation of this data and the creation of contrast materials that will demonstrate myocardial perfusion after intravenous injection are some of the next challenges in these techniques.

Superiority of visual versus computerized echocardiographic estimation of radionuclide left ventricular ejection fraction.

An optimal method for determining left ventricular ejection fraction (LVEF) by echocardiography should be rapid, reliable, and widely applicable in order to be utilized routinely in a busy clinical laboratory. Most methods reported in the literature are reliable in selected, high-quality echocardiograms. Most require off-line computer analysis and are time-consuming and poorly suited to the routine of a busy laboratory. We compared in a blinded manner several echocardiographic methods of LVEF determination with the ejection fraction obtained by equilibrium radionuclide angiography (ERNA) in 44 patients unselected for image quality. Echocardiographic methods included: [1] cubed M-mode formula; [2] Teichholz M-mode formula; [3] subjective estimation of LVEF from two-dimensional echocardiographic videotape; [4] area-length method in one four-chamber view; [5] average of area-length method in three four-chamber views; [6] average of area-length method in four-chamber and two-chamber views (one beat each); [7] subjective estimation from stored videoloop of four-chamber and two-chamber view. In 30 cases M-mode tracings were available for analysis. In only 23 of the 44 patients were the apical views suitable for quantitative analysis. The ERNA ejection fraction was 44 +/- 17% (mean +/- 1 SD). The best echocardiographic correlation with ERNA ejection fraction in each patient subgroup studied was obtained by method 3. We concluded that subjective analysis of the videotaped study by an experienced cardiologist/echocardiographer provided the best estimation of ERNA ejection fraction. More time-consuming and costly computer techniques yielded a worse estimate.

Exercise Doppler echocardiography in patients with mitral prosthetic valves.

Submaximal supine exercise was done by 17 patients with mitral prostheses. Eleven had Björk-Shiley (BS) and six had Starr-Edwards (SE) valves. In 15 patients with normally functioning prostheses, valve area at rest was 2.4 +/- 0.25 cm2 in the BS patients and 1.8 +/- 0.35 cm2 in the SE group (p less than 0.01). In the SE group, peak and mean gradients increased from 8 +/- 1 and 5 +/- 1 mm Hg, respectively, at rest to 22 +/- 5 and 13 +/- 4 mm Hg at peak exercise (mean +/- 1 SD). In the BS group, peak and mean gradients increased from 10 +/- 3 and 5 +/- 2 mm Hg, respectively, at rest to 16 +/- 3 and 10 +/- 3 mm Hg at peak exercise. Peak pressure gradient at peak exercise and the increase in peak gradient with exercise (exercise-resting gradient) were significantly higher in the SE group (p less than 0.05). By plotting the heart rate versus the transmitral gradient during the recovery period, a heart rate-gradient curve was obtained for each type of prosthesis. Doppler echocardiography with moderate supine exercise can be performed in most patients with mechanical prosthesis. Hemodynamic properties (the occlusive character of the SE prosthesis) were brought out by exercise. Doppler echocardiographic measurements during exercise can provide important information, particularly in patients with borderline measurements at rest.

Myocardial perfusion imaging by contrast echocardiography with use of intracoronary sonicated albumin in humans.

Sonicated albumin has been proposed as a near ideal echocardiographic contrast agent with little myocardial toxicity or hemodynamic effect. Its use has not yet been reported in humans, partly because of difficulties in preparation. With use of the newly modified sonication method, 10 ml of 5% albumin was sonicated for 75 s with a 5.0 ml slow infusion of air. This resulted in microbubbles with a mean diameter (+/- SD) of 5 +/- microns). Fourteen patients undergoing routine coronary angiography were studied. One patient had normal coronary arteries; the other 13 had significant coronary artery disease. In a subgroup of nine patients, sonicated albumin and sonicated diatrizoate meglumine sodium (microbubble diameter 9 +/- 3 microns) were injected several minutes apart, using the same technique. Videodensity-time curves were obtained from a region of interest in the myocardium. Corrected peak contrast intensity (baseline contrast intensity subtracted from peak contrast intensity, gray scale U/pixel) for sonicated albumin and for sonicated diatrizoate meglumine sodium was 51 +/- 26 and 52 +/- 19, respectively (p = 0.89). Washout half-time (T1/2) for the two agents was 5.5 +/- 4.5 and 16.0 +/- 12.2 s, respectively (p = 0.01). One patient with unstable angina experienced transient chest pain after repeated albumin injections. No electrocardiographic changes, blood pressure changes or wall motion abnormalities were observed. Administered by intracoronary injection, sonicated 5% albumin is a safe and effective echocardiographic contrast agent for myocardial perfusion imaging, yielding excellent myocardial contrast with physiologic washout time.

Quantitative assessment of the immediate results of coronary angioplasty by myocardial contrast echocardiography.

A low pressure gradient across the residual lesion and a minimal percent residual stenosis are markers of a successful coronary angioplasty. A more physiologic method of assessing the results of coronary angioplasty would involve assessment of myocardial perfusion in the affected coronary bed. Contrast two-dimensional echocardiography provides information about regional myocardial perfusion. To assess the correlation between pre- to postcoronary angioplasty changes in gradient or percent stenosis and the increase in peak contrast intensity, 23 consecutive patients were studied during coronary angioplasty. In 19 of the 23 patients, the coronary angioplasty was successful and in 15 (79%) of the 19, an adequate echocardiographic study was obtained. Mild and transient side effects of echo contrast were observed in 3 of the 15 patients. The gradient across the residual lesions decreased from 52 +/- 12 to 11 +/- 4 mm Hg (mean +/- SD), the diameter of the stenotic lesion decreased from 89 +/- 10 to 25 +/- 16% and corrected peak contrast intensity (peak contrast - baseline contrast in gray level U/pixel) increased from 15 +/- 16 to 50 +/- 26. All these differences were significant at the p less than 0.001 level. Corrected peak contrast intensity correlated exponentially with the decrease in pressure gradient (r = 0.82, p less than 0.001). The correlation curve had a greater increase in peak contrast intensity at gradient decreases greater than 45 mm Hg. Corrected peak contrast intensity did not correlate with decrease in diameter of the stenotic lesion (r = 0.19).

Blinded comparison of an "ultrasound stethoscope" and standard echocardiographic instrument.

We evaluated blinded readings by a physician using a miniature real-time "ultrasound stethoscope" compared with a "standard" echo instrument used by an independent physician. Size of all four cardiac chambers, wall motion, all four valves, thickness of interventricular septum and left ventricular posterior wall, and pericardial effusion were assessed in 66 patients. Each physician estimated whether he had answered the referring question and gave a final diagnosis. The physician using the ultrasound stethoscope correctly assessed chamber size in 87 percent of cases, segmental left ventricular wall motion in 71 percent of segments studied, and wall thickness in 88 percent of cases, and the diagnosis by the ultrasound stethoscope agreed with that made by the standard instrument in 68 percent of cases. The physician with the ultrasound stethoscope detected structural valvular problems (eg, stenosis) in 70 percent of cases but only detected flow abnormalities (eg, regurgitation) in 14 percent of cases. We conclude that (1) an experienced echocardiographer using an ultrasound stethoscope can detect most structural abnormalities found by a standard echocardiographic instrument; (2) chamber size, valvular stenosis, and pericardial effusions were accurately assessed; (3) the ultrasound stethoscope cannot be used to detect valvular regurgitation; and (4) limitations include the lack of freeze-frame, M-mode, hard copy, and Doppler.

Sicca syndrome in mesangial IgA glomerulonephritis.

Schirmer-test, history of conjunctivitis, salivary gland scintigraphy and SSA/SSB (Ro/La) antibodies were evaluated in 24 patients with mesangial IgA glomerulonephritis (IgA-GN), 58 patients with non-IgA-GN and 100 healthy controls. A sicca syndrome (positive Schirmer-test) was found in 46% of patients with IgA-GN and 17% of non-IgA-GN and 8% of controls (p less than 0.001). Only one of the IgA-GN patients volunteered a history of xerosis of the conjunctiva, but upon questioning 17% reported a history of ophthalmological treatment for recurrent conjunctivitis. The observation adds another extrarenal facet to the syndrome of mesangial IgA-GN. Diminished tear production may be another (immune?) abnormality of the oropharyngeal system.