Evaluation of regional myocardial systolic and diastolic function using ECG-gated Sestamibi scintigraphy Preliminary results in patients with and without coronary artery disease

Sestamibi allows ECG-gated acquisition and similarly to radionuclide angiography a time-activity curve from a defined myocardial region can be derived and analysed. Diastolic (peak relaxation velocity) and systolic (per cent thickening) functional parameters from Sestamibi ECG-gated acquisition were obtained; this data were compared in 10 patients with radionuclide angiographic data (peak filling rate and ejection fraction, respectively). A high correlation was found between peak relaxation velocity and peak filling rate (r = 0.792), while no significant correlation was found between thickening and ejection fraction (r=0.577). Sestamibi parameters were calculated in 15 patients with known or suspected coronary artery disease and compared with those obtained in 10 normal subjects. In regions supplied by stenotic vessels the average values of peak relaxation velocity and thickening were significantly lower than those obtained in control subjects in the corresponding vascular territory. The average regional values of the diastolic parameter were significantly lower than the corresponding normal range also in regions with preserved systolic function, i.e. with thickening values within 1SD from the mean value of normals.In conclusion, from the ECG-gated acquisition of Sestamibi regional diastolic and systolic functional parameter may be derived; this completes the spectrum of information that can be obtained by a single injection of tracer.Abbreviations EDc end-diastolic counts - EDV end-diastolic volume - EF% ejection fraction - ESc end-systolic counts - ESV end-systolic volume - PFR peak filling rate - PRV peak relaxation velocity - TH% percent thickening     

Nylon-fiber-induced neutrophil fragmentation

We have investigated the effects of mechanical elution of neutrophils from nylon-wool fiber (NWF) using the scanning electron microscope and biochemical analysis of elution fractions. We have determined that mechanical removal of neutrophils from nylon-wool fiber disrupts neutrophils adherent to nylon-wool fiber and augments release of granules, release of peripheral cytoplasmic fragments, and release of lactic dehydrogenase, a soluble cytoplasmic enzyme. Mechanical shearing of the adherent cell, and not adherence per se, causes the fragmentation. The extent of fragmentation is proportional to the NWF surface area available to neutrophils and is maximal at the temperature for optimal adherence and spreading. Agents that decrease cell spreading (n-ethylmaleimide and cold) diminish fragmentation. Cytochalasin B, an agent that destabilizes the neutrophil cortex, increases fragmentation. Fragmentation may be an important contributing cause of the abnormal morphology, function, and in vivo survival of nylon-wool-fiber procured human neutrophils. The prevention of fragmentation would appear to be necessary to insure the procurement of optimally functioning cells. Elution of NWF-adherent neutrophils in the cold might be a practical way to diminish neutrophil damage during clinical filtration leukapheresis.     

Chronic Oral Anticoagulation and Clinical Outcome in Hospitalized COVID-19 Patients

Cardiovascular Drugs and Therapy - The clinical course of COVID-19 may be complicated by acute respiratory distress syndrome (ARDS) and thromboembolic events, which are associated with high risk of...     

Enhancement of chemotactic factor-stimulated neutrophil oxidative metabolism by leukotriene B4

Leukotriene B4 (LTB4) is a potent primary stimulator of neutrophil chemotaxis, aggregation, and degranulation and induces superoxide production at higher concentrations. In order to determine whether LTB4 modulates neutrophil responses to oxidative stimuli, human neutrophils (PMNs) were incubated with LTB4 prior to stimulation with f-Met-Leu-Phe (fMLP, 10(-7) mol/L), opsonized zymosan (OZ, 250 micrograms/mL), or phorbol myristate acetate (PMA, 32 nmol/L). Superoxide (O2-) production by stimulated PMNs was assessed by the superoxide dismutase-inhibitable reduction of cytochrome c. LTB4 alone did not stimulate O2- production in concentrations below 10(-7) mol/L and had no effect on the O2- assay. In the concentration range of 10(-12) to 10(-8) mol/L, LTB4 did not alter O2- release induced by OZ or PMA. In contrast, LTB4-treated cells demonstrated enhanced O2- production following exposure to fMLP, and in the presence of 10 nmol/LLTB4, generated 180% +/- 41% of O-2 quantities produced by control cells (n = 23). Enhancement was LTB4 dose-dependent, was maximal in the range of 1 to 10 nmol/L LTB4, was not reversed by removal of the lipid from the medium prior to fMLP stimulation, and was not dependent on the presence of Ca++ or Mg++ in the suspending medium. Chemiluminescence of fMLP-stimulated neutrophils was increased to 323% of controls in neutrophils preincubated with 10 nmol/L LTB4. Unlike augmentation of oxidative responses to fMLP seen with other degranulating stimuli, enhancement by LTB4 was not correlated with an increase in 3H-fMLP receptor binding. These results indicate that, in addition to its primary effects on neutrophil function, LTB4 modulates PMN oxidative responses to the chemotactic peptide and, thus, may amplify the release of oxygen metabolites at inflammatory foci.     

In vivo expression of the B7 costimulatory molecule by subsets of antigen-presenting cells and the malignant cells of Hodgkin's disease

The B-lymphocyte/accessory-cell activation antigen B7 (BB1) has been shown in vitro to stimulate T-lymphocyte proliferation and cytokine production via CD28 present on the latter cells. In this study, benign lymphoid tissues, lymphomas, and extralymphoid inflammatory sites were examined immunohistochemically using anti-B7 and other relevant monoclonal antibodies. B7 was expressed by benign transformed germinal center B cells, as it was by B cells of follicular lymphomas. B7 was also expressed by a subpopulation (a mean of 31% to 65%) of macrophages and dendritic cells in a variety of lymphoid tissues. It was present in abundance on all macrophages constituting sarcoid granulomas in lymph nodes. In extralymphoid inflammation, 17% to 35% of macrophages expressed B7 only weakly. Cases of Hodgkin's disease showed expression of B7 by the majority of Reed-Sternberg cells or malignant mononuclear variants, a phenomenon that potentially contributes to the lymphocytic accumulation that is a feature of this condition. CD28+ T cells were seen in all areas where T cells were present. B7+ and CD28+ cells colocalized in, for example, lymphoid follicles, lymph node paracortex, sarcoid granulomas, and Hodgkin's disease tissue, indicating a potential for cellular interaction via these molecules at these sites.     

Normal synthesis and expression of endothelial IIb/IIIa in Glanzmann's thrombasthenia

Glanzmann's thrombasthenia is a bleeding disorder, inherited in an autosomal recessive way and characterized by an absence or deficiency of the platelet glycoprotein (GP) IIb/IIIa complex. Recently, we and others demonstrated that cultured human umbilical vein endothelial cells synthesized a membrane protein complex similar to the platelet GP IIb/IIIa complex. In this article, we demonstrate that endothelial cells isolated from the umbilical vein of a newborn with Glanzmann's thrombasthenia, as compared with normal endothelial cells, show no difference in their ability to synthesize and express this GP IIb/IIIa complex. Our results indicate that Glanzmann's thrombasthenia is not accompanied by an "endotheliopathy."     

A humanised tissue‐engineered bone model allows species‐specific breast cancer‐related bone metastasis in vivo

Bone metastases frequently occur in the advanced stages of breast cancer. At this stage, the disease is deemed incurable. To date, the mechanisms of breast cancer‐related metastasis to bone are poorly understood. This may be attributed to the lack of appropriate animal models to investigate the complex cancer cell–bone interactions. In this study, two established tissue‐engineered bone constructs (TEBCs) were applied to a breast cancer‐related metastasis model. A cylindrical medical‐grade polycaprolactone‐tricalcium phosphate scaffold produced by fused deposition modelling (scaffold 1) was compared with a tubular calcium phosphate‐coated polycaprolactone scaffold fabricated by solution electrospinning (scaffold 2) for their potential to generate ectopic humanised bone in NOD/SCID mice. While scaffold 1 was found not suitable to generate a sufficient amount of ectopic bone tissue due to poor ectopic integration, scaffold 2 showed excellent integration into the host tissue, leading to bone formation. To mimic breast cancer cell colonisation to the bone, MDA‐MB‐231, SUM1315, and MDA‐MB‐231BO breast cancer cells were cultured in polyethylene glycol‐based hydrogels and implanted adjacent to the TEBCs. Histological analysis indicated that the breast cancer cells induced an osteoclastic reaction in the TEBCs, demonstrating analogies to breast cancer‐related bone metastasis seen in patients.     

Right ventricular dysfunction in demand-induced ischemia in patients with isolated right coronary artery disease: a radioisotope study

In ischemic heart disease, the left ventricle has been considered the main target of an imbalance between myocardial oxygen supply and demand. Accordingly, the approach to ischemia has been directed at the evaluation of the left ventricle. The aim of this study was to assess the relative involvement of the left and right ventricle in patients with isolated right coronary artery stenosis. We studied 20 patients with a clinical history of effort angina (15 male, 5 female, mean age 54.1 +/- 6.2) using radionuclide angiography and atrial pacing. Findings were compared with those of 6 normal subjects that were paced at the maximal heart rate of 150 beats/min. Atrial pacing was interrupted because of diagnostic ST segment depression in 8 patients, Wenckebach type atrioventricular block in 1, chest pain without electrocardiographic changes in 4 and the achievement of the maximal prefixed heart rate of 150 beats/minute in 7. With respect to control conditions, during atrial pacing right ventricular ejection fraction declined from 46.8 +/- 6.8% to 37.4 +/- 8.1% (p less than 0.001), while no significant change was observed in left ventricular ejection fraction values (55.2 +/- 4.5% and 51.1 +/- 10.2% respectively). During atrial pacing, left ventricular peak filling rate increased from 1.77 +/- 0.53 to 4.71 +/- 1.8 end-diastolic volumes/second (p less than 0.0001). Qualitative analysis of regional wall motion showed a right ventricular dysfunction in 19/20 patients; this was prevalent in 9 and involving also the left ventricle in 10; an isolated impairment of the left ventricle was observed in 1 patient.(ABSTRACT TRUNCATED AT 250 WORDS)     

High-dose chemoradiotherapy and autologous blood stem cell transplantation in multiple myeloma: results of a phase II trial involving 63 patients

Sixty-three patients with high tumor mass multiple myeloma were treated with high-dose chemotherapy and total body irradiation supported by autologous blood stem cell transplantation. After high-dose therapy, they were monitored for a median of 44 months. Seven patients died early from toxicity. All the other patients, including those whose disease was resistant to previous therapies, showed a tumor mass reduction. At 6 months postengraftment, 40 (71%) of the surviving patients had minimal residual disease and 11 (20%) were in apparent complete remission. During follow-up, 25 out of the 63 (39%) patients relapsed and 16 of these died; 31 (49%) had a sustained remission. The median overall and event-free survival times after transplantation were 59 and 43 months, respectively. The initial serum beta 2-microglobulin value (> or < 2.8 mg/L) and length of previous therapy (> or < 6 courses of chemotherapy) were the only significant prognostic factors. In all surviving patients, blood stem cell autograft provided satisfactory and sustained haematopoietic reconstitution most often within 15 days. High dose chemoradiotherapy followed by autologous blood stem cell transplantation is thus an important therapeutic option for young patients with aggressive multiple myeloma.