[Clinical characteristics of 18 children with chronic nonbacterial osteomyelitis].

Objective: To investigate the clinical features of children with chronic nonbacterial osteomyelitis (CNO), and raise awareness among clinicians. Methods: In this retrospective study, 18 patients with CNO who were diagnosed in Children's Hospital of Fudan University from January 2015 to December 2021 were included. Results: Eighteen children with CNO (12 males, 6 females) were identified. Their age at onset was 9 (5, 11) years, the delay in diagnosis was 2 (1, 6) months, and follow-up-was 17 (8, 34) months. The most common symptoms were fever in 14 children, as well as bone pain and (or) arthralgia in 14 children. In terms of laboratory results, normal white blood cell counts were observed at onset in 17 patients; increased erythrocyte sedimentation rate (ESR) in all patients; increased C reactive protein (CRP) over the normal value in 14 patients. Of the 18 patients, 2 had positive antinuclear antibodies, while none had positive human leukocyte antigen-B27 or rheumatoid factor. Imaging examination revealed that all the patients had symmetrical and multifocal skeletal lesions. The number of structural lesions detected by imaging investigation was 8 (6, 11). The most frequently affected bones were tibia in 18 patients and femur in 17 patients. Bone biopsy was conducted in 14 patients and acute or chronic osteomyelitis manifested with inflammatory cells infiltration were detected. Magnetic resonance imaging (MRI) found bone lesions in all the patients and bone scintigraphy were positive in 13 patients. All the patients were treated with nonsteroidal anti-inflammatory drugs, among whom 10 cases also treated with oral glucocorticoids, 9 cases with traditional disease modifying anti-rheumatic drugs, 8 cases with bisphosphonates and 6 cases with tumor necrosis factor inhibitors. The pediatric chronic nonbacterial osteomyelitis disease activity score, increased by 70% or more in 13 patients within the initial 6-month follow-up. Conclusions: The clinical manifestations of CNO are lack of specificity. The first symptom of CNO is fever, with or without bone pain and (or) arthralgia, with normal peripheral blood leukocytes, elevated CRP and (or) ESR. Whole body bone scanning combined with MRI can early detect osteomyelitis at subclinical sites, and improve the diagnostic rate of CNO.

High-efficiency gene transfer to autologous rabbit jugular vein grafts using adenovirus-transferrin/polylysine-DNA complexes.

Within the first year, 15-20% of coronary artery saphenous bypass vein grafts (SVGs) occlude because of thrombosis or progressive intimal hyperplasia. One potential new strategy to reduce this complication would be to introduce antithrombotic or antiproliferative genes in vein grafts before implantation. The success of this approach requires an efficient DNA delivery system. In the present study we tested the feasibility of using adenovirus-transferrin/polylysine-DNA complexes (TfAdpl/DNA) to achieve high-efficiency gene transfer into vascular interposition vein grafts. All studies used the Escherichia coli LacZ (beta-galactosidase [beta-Gal]) reporter gene under the control of the cytomegalovirus (CMV) earlier promoter and enhancer (pCMV/LacZ). Autologous rabbit jugular vein segments were incubated ex vivo for 60 min in a solution of TfAdpl/DNA complexes (1.2 x 10(10) biotinylated adenovirus particles, 2,430 ng of streptavindylated polylysine. 10 micrograms of plasmid DNA, and 9 micrograms of transferrin-polylysine per ml), and then reimplanted across the ligated right carotid artery. Control veins were incubated in TfAdpl solution in which DNA was omitted. A total of six grafts were treated with TfAdpl/DNA, and two grafts were treated with TfAdpl. Veins were harvested 3 (n = 3) and 7 (n = 3) days later and beta-Gal activity was determined by X-Gal chromogen staining. All six TfAdpl/DNA-treated grafts stained intensely blue, whereas control grafts were negative. Microscopic examination of serial sections revealed intracellular blue granules consistent with beta-Gal activity to be present in all of the endothelial cells and in numerous medial and advential cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of vein valves in the development of arteriosclerosis in venoarterial grafts in the rabbit.

Coronary saphenous vein grafts in human beings have a more limited long-term patency rate than internal thoracic artery grafts, primarily because of more rapid development of arteriosclerosis. The factors responsible for this increased susceptibility are not completely understood. To test the hypothesis that vein valves may influence this process, we studied 48 hypercholesterolemic rabbits with jugular vein grafts interposed into the carotid arterial circulation. In 24 animals (group A), the vein segments did not contain a vein valve. In the other 24 animals (group B), a vein valve was present. Both groups were further divided in four subgroups of six to be put to death at 2, 4, 6, and 8 weeks after the operation. All animals were fed a 2% cholesterol diet. At postmortem examination, alternate 2 mm sections were either stained with hematoxylin and eosin for histologic and morphometric studies or frozen in liquid nitrogen for immunohistochemistry and in situ hybridization studies. Proliferating cell nuclear antigen immunostaining was used to study cell proliferation. Wall thickness of vein grafts increased with time. During the first 2 weeks intimal and medial thickening was primarily due to an increase in numbers of cells. Between 2 and 6 weeks further intimal and medial thickening occurred, but without additional increase in cell numbers. After 6 weeks, foam cells and lipid deposits started to appear. By 8 weeks, changes identical to those seen in arteriosclerotic plaques in human beings were evident. These changes developed sooner and with more intensity in group B animals (p < 0.01 to 0.001), and they developed faster and with more severity in segments of vein located distal to the valve than in the segments located proximal to the valve (p < 0.001). This is the first controlled experiment demonstrating that the presence of valves in the vein segments is associated with augmented and accelerated intimal changes leading to vein atheromatosis.

Perivascular delivery of a nitric oxide donor inhibits neointimal hyperplasia in vein grafts implanted in the arterial circulation.

OBJECTIVE: Nitric oxide has been reported to reduce intimal hyperplasia as a response to arterial injury. This study was designed to assess the possible effect of perivascular application of a nitric oxide donor on neointimal proliferation occurring in veins exposed to the dynamics of the arterial circulation in a hypercholesterolemic rabbit model. METHODS: Autologous jugular vein grafts were implanted in the carotid circulation of 20 hypercholesterolemic rabbits. A mixture of a biodegradable polymer and the nitric oxide donor, spermine/nitric oxide, which releases nitric oxide with a half-life of 39 minutes, was applied periadventitially at the time of implantation. Controls were veins bathed in saline solution, polymer alone, and polymer plus the carrier vehicle spermine without nitric oxide. Animals (n = 5 in each group) were put to death on day 28 for morphometric analysis, cell count, and immunohistochemical staining. RESULTS: Treatment with perivascular nitric oxide donor significantly decreased wall thickness (126 +/- 24 microm vs 208 +/- 45 microm, p = 0.0017) and area (124 +/- 22 microm2/microm vs 211 +/- 37 microm2/microm, p = 0.005). With the carrier vehicle spermine alone, there was a trend toward reduced intimal thickness, but the change was not statistically significant. In the grafts treated with nitric oxide donor, expression of insulin-like growth factor, fibroblast growth factor, thrombospondins, fibronectin, and tenascin was reduced. CONCLUSION: The periadventitial delivery of nitric oxide donor produces a reduction of neointimal hyperplasia in veins implanted in the arterial circulation. The mechanism of action is not entirely clear, but the reduction cannot be explained on the basis of decreased cell proliferation alone. Other possibilities are modulation of protein synthesis of vascular smooth muscle cells and production of extracellular matrix components.

Expression of cell adhesion molecules in human cardiac allograft rejection.

Adhesion of leukocytes to vascular endothelial cells is a critical step in a variety of inflammatory conditions. We studied the expression and distribution of intercellular adhesion molecule-1 (ICAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1) in frozen sections of 83 endomyocardial biopsy specimens from human allograft hearts using monoclonal antibodies and an avidin-biotin complex-alkaline phosphatase staining technique. Cases with cellular or humoral rejection and Quilty lesions were studied. Staining was graded from 0 to 3+ in lymphocytes and in capillary, arterial, venular, and endocardial endothelial cells. Expression of ICAM-1 in capillaries increased with the severity of cellular rejection and was prominent in humoral rejection. ICAM-1 was also expressed in lymphocytes in proportion to the degree of rejection. Little or no ELAM-1 expression was noted. In Quilty lesions the intensity of ICAM-1 expression was similar to that of mild-to-moderate rejection. Thus adhesion molecule expression can be identified in endomyocardial biopsy specimens of patients with rejection, suggesting a role for adhesion molecules in the process of rejection. These findings may prove useful in monitoring rejection and its response to therapy and in developing specific antisera directed against these molecules.

Cytokine expression and endothelial cell and lymphocyte activation in human cardiac allograft rejection: an immunohistochemical study of endomyocardial biopsy samples.

We used monoclonal antibodies and immunohistochemical staining of frozen tissue sections to study the expression of cytokines in human cardiac allograft rejection. The 113 endomyocardial biopsy samples were stained for interleukin (IL)-2, IL-6, and interferon-gamma. The findings were compared to expression of the endothelial cell adhesion molecule ICAM-1, and the lymphocyte receptor for the adhesion molecule VCAM-1, VLA-4. Four biopsy samples from patients with idiopathic cardiomyopathy served as controls. IL-2 was not expressed in lymphocytes of controls and only occasionally in mild or moderate cellular rejection, humoral rejection, and Quilty lesions. IL-2 expression was prominent in severe cellular rejection. Interferon-gamma expression increased in proportion to the severity of cellular rejection and was not expressed in other conditions. IL-6 staining, which was only observed in occasional cases, was mild. Cytokine and adhesion molecule expression tended to increase with the severity of cellular rejection. This study shows that cytokine expression can be documented in human allograft endomyocardial biopsy samples with immunohistochemical techniques. The findings support the concept of an important role for cytokines in human cardiac allograft rejection.

Pathogenesis of Quilty lesion in cardiac allografts: relationship to reduced endocardial cyclosporine A.

BACKGROUND: Endocardial lymphocytic infiltrates, known as Quilty effect, are a common finding of uncertain pathogenesis in cardiac allografts. Quilty effect was not observed before the use of cyclosporine A for immunosuppression and is not generally regarded as a manifestation of rejection. We hypothesized that the endocardial localization of Quilty effect may be related to a relative absence of cyclosporine A in this region. METHODS: We used an indirect immunofluorescence staining method with rabbit polyclonal anti-cyclosporine A antibodies to detect cyclosporine A in fresh frozen sections of 27 cardiac allograft endomyocardial biopsies. Staining was graded 0 to +3. Negative controls were from untreated transplant candidates and from biopsies with the primary antibody omitted. RESULTS: On comparison of endocardial and myocardial fluorescence in biopsy specimens from patients treated with cyclosporine A, there was less endocardial (0.7 +/- 1.1, p < 0.0001) than myocardial (2.2 +/- 0.5) staining. However, in biopsy specimens with Quilty effect (n = 12), this difference was significantly greater (endocardial = 0.2 +/- 0.6 versus myocardial = 2.3 +/- 0.5; p = 0.005) than in specimens without Quilty effect (n = 10) (endocardial = 1.4 +/- 1.2 versus myocardial = 2.1 +/- 0.6; p = 0.7). Endocardial thickness as measured by ocular micrometry was significantly greater in regions with (32 +/- 19 microns) than without (7 +/- 4 microns) Quilty effect, with involved regions showing increased connective tissue (p < 0.0001). In patients with and without Quilty effect, no differences in donor or recipient demographics, prevalence of diabetes, or plasma cyclosporine A levels were found. CONCLUSIONS: Although it has been postulated that Quilty effect is due to the presence of cyclosporine A in cardiac tissue (toxic effect or immunologic reaction), these data suggest that Quilty effect is related to reduced endocardial presence of cyclosporine A, leading to localized, contained, and usually not clinically significant endocardial rejection.

[Syndrome differentiation patterns for peri-operative coronary heart disease patients of coronary artery bypass graft].

OBJECTIVE: To explore the patterns of Syndrome Differentiation of coronary artery bypass graft (CABG) on the peri-operative coronary heart disease (CHD) patients. METHODS: One week after operation, thirty-seven CHD patients, who received CABG of internal mammary artery or great saphenous vein under conventional general anesthesia with low or middle temperature extracorporeal circulation were differentiated as various syndromes, the pre- and post-operational ECG, color Doppler echocardiography as well as during and after operation. The hemodynamic parameters were monitored. RESULTS: In the CHD patients, 64.9% were differentiated as Qi-Yin deficiency, 67.6% were complicated with Phlegm Syndrome and 62.2% with Stasis in blood, suggesting that Qi-deficiency, phlegm and stasis are the basic pathogenesis in patients after CABG. Moreover, the peri-operative Syndrome was correlated with the condition of coronary arterial lesions, heart and lung functions before operation, and the time for extracorporeal circulation during the operation. CONCLUSION: TCM Syndrome Differentiation conducting in peri-operative stage might be useful to explore the patterns of Syndrome alteration which provided a basis for preventing peri-operational complication and elevating success rate of operation.

Flow measurements in an aortocoronary bypass graft casting.

Flow visualization and pressure measurements were carried out in a singel valve saphenous vein casting which was made from a saphenous vein segment obtained from a bypass patient at Cedars Sinai Medical Center. Dye was injected to understand the flow around the valve. The dye showed very complex flow patterns around the valve and in the valve sinus, and the cavity formed by a ligated branch. For steady flow, pressure drops across the valve were 0.72, 2.0 and 6.3 mmHg for the physiological flow rates of 45, 84, and 169 ml/min, respectively. Overall pressure drop across the casting (compared to Poiseuille flow for a straight tube) increased with the flow rate, being 130 to 290 percent higher over this flow rate range. In the case of pulsatile flow, pressure drops across the valve were 0.95 and 3.0 mmHg for the flow rates of 47 and 87 ml/min which were 26 and 43 percent higher than those of steady flow. Overall pressure drop was 220 and 360 percent higher for those flow rates compared to Poiseuille flow. The measured spatial pressure distributions along the casting and flow visualization indicated the global nature of the flow field with the accelerated flow through the valve separating and reattaching downstream along the wall in the pressure recovery region. Atherosclerosis may be prone to occur in the lower shear region along the wall beyond the valve tip in the reattachment region, as we have observed in vivo in rabbit experiments.