Aortic dissection with diastolic prolapse of intimal flap into left ventricle.

Ascending aortic dissection is often a catastrophic condition. Dissection into the commissures or into an aortic valve leaflet may lead to leaflet avulsion and valvular insufficiency due to a flail valve. We present an image report describing an important and life-threatening complication due to the movement of a partially dehisced intimal aortic flap into the left ventricle causing aortic valve insufficiency in a patient with acute dissection of the ascending aorta.     

Effects of human FLT3 ligand on myeloid leukemia cell growth: heterogeneity in response and synergy with other hematopoietic growth factors

A novel hematopoietic growth factor for primitive hematopoietic progenitor cells, the ligand for the flt3/flk2 receptor, (FL), has been recently purified and its gene has been cloned. In the present study, we investigated the effects of FL on the proliferation and differentiation of normal and leukemic myeloid progenitor cells. We demonstrate that FL is a potent stimulator of the in vitro growth of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin- 3 (IL-3), or G-CSF-dependent granulocyte-macrophage committed precursors from Lin- CD34+ bone marrow cells of normal donors. By contrast, FL does not affect the growth of erythroid-committed progenitors even in the presence of erythropoietin. The effect of FL on the proliferation and on the in vitro growth of clonogenic leukemic precursor cells was studied in 54 acute myeloid leukemia (AML) cases. Fresh leukemia blasts from 36 of 45 patients with AML significantly responded to FL without any relation to the French-American-British (FAB) subtype. FL stimulated the proliferation of leukemic blasts in a dose-dependent fashion. Synergistic activities were seen when FL was combined with G-CSF, GM-CSF, IL-3, or stem cell factor (SCF). FL as a single factor induced or increased significantly colony formation by clonogenic precursor cells from 21 of 24 patients with AML. In the presence of suboptimal and optimal concentrations of G-CSF, GM-CSF, IL3, SCF, or a combination of all factors, FL strongly enhanced the number of leukemic colonies (up to 18-fold). We also evaluated the induction of tyrosine phosphorylated protein on FL stimulation in fresh AML cells. We demonstrate that, on FL stimulation, a band of phosphorylated protein(s) of about 90 kD can be detected in FL- responsive, but not in FL-unresponsive cases. This study suggests that FL may be an important factor for the growth of myeloid leukemia cells, either as a direct stimulus or as a synergistic factor with other cytokines.     

Impairment of chemoattractant-stimulated hexose uptake in neonatal neutrophils

Neonatal neutrophils (polymorphonuclear leukocytes [PMN]) exhibit a well-documented deficiency in chemotaxis, the nature of which has not been fully elucidated. To determine whether impaired ability of neonatal PMN to increase hexose uptake in response to chemoattractants could contribute to this defect, we compared uptake of 2-deoxy-D- glucose (2-DOG) in stimulated versus resting PMN from neonates (cord blood) and healthy adults. Compared with unstimulated values; N-formyl- methionyl-leucyl-phenylalanine (fMLP) (optimal at 10 nmol/L) caused a threefold to fourfold increase in 2-DOG uptake by adult PMN. Unstimulated 2-DOG uptake by neonatal PMN was slightly higher than that for adult cells, but fMLP caused only a minimal (less than twofold) increase, and optimally stimulated uptake was significantly lower than for adult PMN (P < .01 for adult versus neonatal stimulated uptake; n = 6). Findings were similar when ionomycin or C5a was used as a stimulus. Optimal fMLP stimulation of adult PMN was associated with a marked decrease in the Km for 2-DOG uptake, from 0.74 +/- 0.11 to 0.23 +/- 0.03 mmol/L (delta Km = -0.51 +/- 0.12 mmol/L; n = 6). In contrast, there was relatively little fMLP-induced change in the Km for uptake of 2-DOG by neonatal PMN (from 0.44 +/- 0.04 mmol/L to 0.32 +/- 0.019 mmol/L n = 6); delta Km = -0.12 +/- 0.04 mmol/L; P = .011 for adult versus neonatal delta Km. Stimulation with fMLP was not accompanied by a significant change in the Vmax for 2-DOG uptake with either adult or neonatal PMN, and the respective values for Vmax were similar. We conclude that the chemoattractant-induced increase in hexose uptake by PMN is deficient in neonates compared with adults and that this deficiency involves mechanisms that determine the Km for this process. This impairment may contribute to defective chemotaxis in neonatal PMN.     

CD34 expression is regulated reciprocally with adhesion molecules in vascular endothelial cells in vitro

Freshly cultured vascular endothelial cells express the CD34 antigen in a diffuse cell surface pattern with some concentration on microvilli. Expression is downregulated with proliferation in continuous culture and undetectable after nine population doublings but can be maintained by restraining cell proliferation and promoting cell contact. Expression of CD34 at the antigen and mRNA levels on early passage cells is rapidly downregulated by interleukin-1 beta (IL-1 beta), interferon-gamma (INF-gamma), and tumor necrosis factor-alpha (TNF- alpha) under conditions in which these ligands upregulate the adhesion molecules: endothelial leukocyte adhesion molecule 1 (ELAM-1) and intracellular adhesion molecule 1 (ICAM-1). This reciprocal pattern of expression and the topographic distribution of CD34 molecules on the lumenal interdigitated microprocesses of adjacent endothelial cells in vivo suggest that CD34 might have a negative modulating role on adhesion functions of endothelia.     

Serum level of lipoprotein (a) is inversely associated with the development of coronary collateral circulation

BACKGROUND: This study sought to determine the relationship between serum lipoprotein (a) levels and angiographically visible coronary collateral circulation and to evaluate whether lipoprotein (a) exerts any effect on vascular endothelial cell growth factor. METHODS: The study population included 60 patients (39 men, mean age 59+/-13 years) with angiographically documented total occlusion in one of the major coronary arteries. Development of collaterals was classified by Rentrop's method. Patients were defined as having poorly developed collaterals for grades 0 and 1 (group 1), or well-developed collaterals for grades 2 and 3 (group 2). Serum lipoprotein (a) and vascular endothelial cell growth factor levels were determined by enzyme-linked immunosorbent assay. RESULTS: In group 1, lipoprotein (a) levels were significantly higher and vascular endothelial cell growth factor levels were significantly lower than in group 2 (34+/-19 vs. 20+/-12 mg/dl, P<0.001, and 2.5+/-0.7 vs. 3.4+/-0.8 ng/dl, P<0.001, respectively). Poorly developed collaterals were significantly more frequent in patients with lipoprotein (a) levels >or=30 mg/dl than in patients with levels <30 mg/dl (72 vs. 37%, P=0.008). A strong negative correlation was observed between lipoprotein (a) and vascular endothelial cell growth, factor (r=-0.708, P<0.0001). Multivariate analysis revealed that a high level of lipoprotein (a) negatively affected the development of collaterals, whereas the duration of angina had a positive effect. CONCLUSION: This study demonstrated for the first time that the high level of lipoprotein (a) negatively affects the formation of coronary collateral vessels in human beings. Reduced production or bioactivity of vascular endothelial cell growth factor caused by high levels of lipoprotein (a) may be the possible responsible mechanisms of hyperlipoprotein (a)-related poor collateral formation.     

Does p-wave dispersion predict the atrial fibrillation occurrence after direct-current shock therapy?

Supraventricular tachycardia attacks, including atrial fibrillation (AF), occur after both external and internal cardioversions. These attacks of atrial fibrillation after direct-current (DC) shock may be related to hemodynamic impairment, thromboembolic events, or enhanced electrical instability of the ventricular and atrial myocardium, especially in predisposed patients. In this study, the authors aimed to show the importance of P-wave dispersion (PWD), which lead the atrium to fibrillate, in predicting post-DC shock AF after external cardioversion. Thus physicians may be able to choose the patients with high risk for AF occurrence and apply some other therapeutic modalities to those patients. The authors identified 18 patients in whom an AF attack was induced by urgent or elective cardioversion for a ventricular tachycardia attack and compared these patients with a control group composed of 40 patients without AF in regard to some clinical, echocardiographic, and electrocardiographic parameters. Left atrial diameters were greater (4.3+/-0.3 vs 3.5+/-0.5 cm, p = 0.001), left ventricular ejection fractions (LVEF) were lower (45.2+/-8.2 vs 54.9+/-7.5, p = 0.001), the energy needed for successful cardioversion was higher (166.6+/-59.4 vs 80.8+/-51.6 J, p = 0.001), and P max (135.2+/-7.4 vs 118.7+/-10.5 ms, p = 0.001) and PWD (53.8+/-12.2 vs 23.8+/-9.5 ms, p = 0.001) values were higher in patients with AF when compared to those without AF. Thus, the patients with higher PWD values had a greater risk for development of AF after a DC shock.     

The value of urine specific gravity in detecting diabetes insipidus in a patient with uncontrolled diabetes mellitus: urine specific gravity in differential diagnosis

When a patient with diabetes mellitus presents with worsening polyuria and polydipsia, what is a sensible, cost-effective approach? We report the unique coincidence of type 2 diabetes mellitus and diabetes insipidus. A 46-year-old woman with poorly controlled type 2 diabetes complained of polyuria with a daily output of 5 L. Although urinalysis demonstrated significant glucosuria, diabetes insipidus was suspected owing to a low urine specific gravity (1.008). The low specific gravity persisted during a water deprivation test. Ultimately, diabetes insipidus was confirmed when urine specific gravity and urine osmolality normalized following desmopressin administration. This case emphasizes the importance of accurately interpreting the urine specific gravity in patients with polyuria and diabetes mellitus to detect diabetes insipidus.     

Relation between sympathetic overactivity and left atrial spontaneous echo contrast in patients with mitral stenosis and sinus rhythm

BACKGROUND: Spontaneous echo contrast (SEC) is common in patients with mitral stenosis (MS) and presence of SEC in left atrium (LA) is associated with a higher risk of thromboembolism. Recently, an increase in activation of platelets was demonstrated in patients with SEC raising the hypothesis that platelets are involved in the pathogenesis of SEC. In this study, we evaluated effects of autonomic nervous system activity on SEC formation in patients with rheumatic MS and sinus rhythm by heart rate variability analysis. METHODS AND RESULTS: Twenty-six patients with LASEC were compared with 28 patients without LASEC. Mean heart rate, low frequency (LF) and low frequency/high frequency (LF/HF) ratio were significantly higher, standard deviation of all NN (SDNN), root mean square of successive differences (RMSSD), number of NN intervals that differed by more than 50 ms from adjacent interval divided by the total number of all NN intervals (PNN50) and high frequency (HF) values were lower in the patients with LASEC. A standard deviation of all NN intervals <90ms separated the patients with LASEC from control subjects with a sensitivity of 77% and specificity of 90%; a low frequency >79.5 with a sensitivity of 92% and specificity of 90; a low frequency/high frequency ratio >3.7 with a sensitivity of 96% and specificity of 90%. A left atrial diameter >4.3 cm increased the LASEC formation by 3.0 folds, HR >78 beats/min by 6.4 folds, standard deviation of all NN intervals <90 ms by 9.2 folds, a low frequency/high frequency ratio >3.7 by 6.4 folds, sP-selectin>142 by 5.8 folds. Variables affecting sP-selectin levels were LA diameter, mitral valve area, transmitral mean gradient, left ventricular ejection fraction, the presence of mitral regurgitation, HR, standard deviation of all NN intervals, low frequency, high frequency and low frequency/high frequency ratio. CONCLUSION: Sympathetic overactivity and reduced heart rate variability are important determinants for LASEC formation and increased s-P selectin levels. Therefore, platelet activation via increased sympathetic activity may play an important role in pathogenesis of LASEC.