Detailed immunotyping was carried out on 21 direct myeloma bone marrow aspirates and eight human myeloma cell lines. Four previously untreated common acute lymphoblastic leukemia antigen (CALLA)-positive myeloma patients were identified and six of eight cell lines (75%) were also positive. CALLA positivity, as part of an immature B phenotype, was found to correlate with very aggressive clinical disease: median survival six months v 56 months for the CALLA-negative group. 相似文献
The PET tracer [11C]5-hydroxytryptophan ([11C]5-HTP), which is converted to [11C]5-hydroxytryptamine ([11C]5-HT) by aromatic amino acid decarboxylase (AADC), is thought to measure 5-HT synthesis rates. But can we measure these synthesis rates by kinetic modeling of [11C]5-HTP in rat? Male rats were scanned with [11C]5-HTP (60 minutes) after different treatments. Scans included arterial blood sampling and metabolite analysis. 5-HT synthesis rates were calculated by a two-tissue compartment model (2TCM) with irreversible tracer trapping or Patlak analysis. Carbidopa (inhibitor peripheral AADC) dose-dependently increased [11C]5-HTP brain uptake, but did not influence 2TCM parameters. Therefore, 10 mg/kg carbidopa was applied in all subsequent study groups. These groups included treatment with NSD 1015 (general AADC inhibitor) or p-chlorophenylalanine (PCPA, inhibitor of tryptophan hydroxylase, TPH). In addition, the effect of a low-tryptophan (Trp) diet was investigated. NSD 1015 or Trp depletion did not affect any model parameters, but PCPA reduced [11C]5-HTP uptake, and the k3. This was unexpected as NSD 1015 directly inhibits the enzyme converting [11C]5-HTP to [11C]5-HT, suggesting that trapping of radioactivity does not distinguish between parent tracer and its metabolites. As different results have been acquired in monkeys and humans, [11C]5-HTP-PET may be suitable for measuring 5-HT synthesis in primates, but not in rodents. 相似文献
To investigate the safety and efficacy of inferior vena caval (IVC) balloon occlusion for preload alteration in humans, 13 patients with dilated cardiomyopathy were studied before and during repeated (total of 78) IVC occlusions. Left and right ventricular (LV and RV) micromanometer pressures were simultaneously measured and M-mode and 2-D echocardiograms were recorded at end expiration. Complications were limited to abdominal discomfort in 2 patients. With IVC occlusion, RV collapse fluoroscopically shifted the heart toward midline and ventricular septal motion was frequently disordered. Significant (p = 0.001) changes occurred in RV and LV systolic peak pressures (from 19 +/- 6 to 12 +/- 5 mm Hg and from 129 +/- 34 to 109 +/- 25 mm Hg, respectively). LV and RV end-diastolic pressures also decreased significantly (from 18 +/- 7 to 6 +/- 6 mm Hg and from 5 +/- 3 to 2 +/- 2 mm Hg, respectively) (both p less than or equal to 0.0055). Similarly, LV end-diastolic diameter decreased 13% (from 61 +/- 11 to 53 +/- 12 mm, p = 0.0002). Mean heart rate did not change significantly (from 76 +/- 19 to 78 +/- 21 beats/min). Thus, IVC balloon occlusion provides a safe method of repeatedly altering loading conditions in humans. This approach allows for acquisition of important information regarding cardiac chamber dynamics while minimizing the effects of reflex mechanisms and avoiding use of pharmacologic agents. 相似文献
The hemodynamics of the supine and upright exercise response in 16 symptomatic women with mitral valve prolapse (Group I) was compared with that in 8 asymptomatic normal control women (Group II). All subjects had supine and upright echocardiography and phonocardiography at rest and none demonstrated mitral regurgitation. All participants then underwent same day graded bicycle exercise, with simultaneous radionuclide angiography in both the upright and the supine posture. Catecholamines were measured, and a variety of volumetric and hemodynamic data were obtained. Group I (patients with mitral valve prolapse) demonstrated a reduced exercise tolerance, especially during upright exercise, as measured by both total exercise duration and maximal work load achieved. Mean total catecholamine measurements were similar between the two study groups at comparable mean heart rate, mean blood pressure and mean rate-pressure (double) product. No difference was observed in the ratio of right to left ventricular stroke counts at rest or during exercise regardless of posture, suggesting that exercise-induced mitral regurgitation did not occur. A difference was noted, however, in left ventricular end-diastolic volume index. At rest, Group I patients exhibited a 42% decrease in this index when sitting upright, and this difference from supine values persisted at submaximal (300 kpm/min) and peak work loads (34 and 29% difference, respectively). This contrasted with the control subjects whose upright end-diastolic volumes at rest, at 300 kpm/min and at peak exercise were reduced 21, 10 and 3%, respectively, compared with supine values. Cardiac index measurements reflected the reduced left ventricular end-diastolic volume observed.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
The purposes of this study were to determine the prevalence of angiographically significant renal artery stenosis in a patient population referred for diagnostic cardiac catheterization and to develop a model that predicts the highest-risk subset of patients who have significant renal artery narrowing. A prospective validation cohort study was undertaken in a referral-based university hospital. After left ventriculography, abdominal aortography was performed to screen for the presence of renal artery disease. A convenience sample of 1,302 of 1,651 consecutive patients undergoing diagnostic cardiac catheterization were enrolled in the study. Of the 1,302 abdominal aortograms performed, 1,235 (95%) were deemed of adequate quality for the evaluation of renal artery anatomy. Renal artery disease was identified in 30% of the patients. Insignificant renal artery stenosis was found in 187 (15%) and significant (greater than or equal to 50% diameter narrowing) stenosis was found in 188 (15%). Significant unilateral disease was present in 11%, and bilateral disease was present in 4%. By univariable and multivariable logistic regression analysis, the association of both clinically and catheterization-derived variables with renal artery disease was assessed. Multivariable predictors included age, severity of coronary artery disease, congestive heart failure, female gender, and peripheral vascular disease. Hypertension was not an associated variable. These data reveal the previously undetected high prevalence of renal artery disease in patients undergoing cardiac catheterization and provide clinical and angiographic features that assist in predicting its presence. 相似文献
We sought to compare the responses of patients with pulmonary hypertension from primary and secondary causes (PPH and SPH, respectively) to inhaled nitric oxide (iNO) in the cardiac catheterization laboratory.
BACKGROUND
Pulmonary hypertension can lead to right ventricular pressure overload and failure. Although vasodilators are effective as therapy in patients with PPH, less is known about their role in adults with SPH. Inhaled nitric oxide can accurately predict the response to other vasodilators in PPH and could be similarly utilized in SPH.
METHODS
Forty-two patients (26 to 77 years old) with pulmonary hypertension during cardiac catheterization received iNO. Demographic and hemodynamic data were collected. Their response to iNO was defined by a decrease of ≥20% in mean pulmonary artery (PA) pressure or pulmonary vascular resistance (PVR).
RESULTS
Mean PA pressures and PVR were lower during nitric oxide (NO) inhalation in all patients with pulmonary hypertension. Seventy-eight percent of patients with PPH and 83% of patients with SPH were responders to iNO. A trend was seen toward a greater response with larger doses of NO in patients with SPH. Nitric oxide was a more sensitive predictor of response (79%), compared with inhaled oxygen (64%), and was well tolerated, with no evidence of systemic effects. Elevation in right ventricular end-diastolic pressure appeared to predict poor vasodilatory response to iNO.
CONCLUSIONS
Nitric oxide is a safe and effective screening agent for pulmonary vasoreactivity. Regardless of etiology of pulmonary hypertension, pulmonary vasoreactivity is frequently demonstrated with the use of NO. Right ventricular diastolic dysfunction may predict a poor vasodilator response. 相似文献
We have previously shown that normal-density human peripheral blood eosinophils transcribe and translate mRNA for granulocyte-macrophage colony-stimulating factor (GM-CSF) and that the intracellular distribution was granular as assessed by light microscopy immunocytochemistry. The present study was conducted to confirm this apparent association between GM-CSF and the crystalloid granule using a subcellular fractionation method for human eosinophils and immunogold electron microscopy (EM). Highly purified (> 99%, by negative selection using anti-CD16 immunomagnetic microbeads) human peripheral blood eosinophils were obtained from four asthmatic subjects (not taking systemic medication), homogenized and density fractionated (5 x 10(7) cells/subject) on linear Nycodenz gradients. Twenty-four fractions were collected from each cell preparation and analyzed for marker enzyme activities as well as total protein. Dot blot analysis with specific monoclonal antibodies (MoAbs) was used to detect the eosinophil granule proteins major basic protein (MBP) and eosinophil cationic protein (ECP). An anti-CD9 MoAb was used as an eosinophil plasma membrane marker. Lactate dehydrogenase (LDH) was used as a cytosolic marker. Immunoreactivity for GM-CSF was detected by a specific enzyme-linked immunosorbent assay using a polyclonal antihuman GM-CSF antibody and confirmed by dot blot. GM-CSF coeluted with the cellular fractions containing granule markers (MBP, ECP, eosinophil peroxidase, hexosaminidase, and arylsulphatase), but not those containing cytoplasm (LDH+) or membrane (CD9+) markers. EM examination of pooled fractions associated with the peak of GM-CSF immunoreactivity confirmed that they contained crystalloid and small granules, but not plasma membrane. In addition, quantification, using immunogold labeling with an anti/GM-CSF MoAb, indicated preferential localization of gold particles over the eosinophil granule cores of intact cells. Thus, our results indicate that GM-CSF resides as a granule-associated, stored mediator in unstimulated human eosinophils. 相似文献