Percutaneous therapy of structural heart disease: pediatric disease

Interventional therapy of congenital heart lesions at cardiac catheterization has greatly increased during the past decade. At the authors' institution, the frequency of such procedures among catheterizations has increased from 5% to more than 60%. The variety of lesions so treated continues to expand and equipment continues to improve. These procedures may be divided into 2 groups, namely (1) those involving balloon dilation of stenotic valves and vessel obstructions with stent placement being increasingly used in the latter and (2) those involving occlusion of lesions with (a) coils, such as aortopulmonary collaterals, patent ductus arteriosi and coronary artery fistulae and (b) umbrella devices, such as atrial and ventricular septal defects. These have replaced surgery as the initial procedure of choice in many lesions including valvar pulmonary and aortic stenoses, and postoperative aortic coarctation in young patients. In addition, use of the double-umbrella device even in noncongenital lesions appears promising.     

MR arthrography of the shoulder

Although conventional MR imaging allows direct visualization of major anatomic structures, smaller intraarticular structures, including the glenoid labrum, glenohumeral ligaments, and articular surface of the rotator cuff tendon can be difficult to evaluate in the absence of a joint effusion. The authors review the techniques employed in performing MR arthrography, imaging characteristics of MR arthrography, and diagnostic utilization of the technique. Suggested indications are provided.     

Interleukin-4 or interleukin-10 expressed from adenovirus-transduced syngeneic islet grafts fails to prevent beta cell destruction in diabetic NOD mice

BACKGROUND: We performed ex vivo adenoviral gene transfer in a mouse pancreatic islet transplant model to test the efficacy of this expression system. We then determined whether adenoviral-mediated expression of mouse interleukin (IL) 4 or IL-10 from transduced syngeneic islet grafts could prevent disease recurrence in diabetic nonobese diabetic (NOD) mice. METHODS: An adenoviral vector expressing beta-galactosidase (AdCMV betaGal) was used to transduce BALB/c islets (2.5 x 10(3) plaque-forming units/islet), which were analyzed for glucose responsiveness, islet cell recovery, and efficiency of gene transfer. In vivo function and reporter gene expression were examined with AdCMV betaGal-transduced islet grafts in alloxan-induced diabetic syngeneic recipients. Adenoviruses expressing either IL-4 or IL-10 were used in a similar fashion to infect NOD islets, which were characterized in vitro, as well as transplanted into diabetic syngeneic recipients. RESULTS: In vitro functional studies showed no significant difference between control or transduced islets, with 50+/-4% of AdCMV betaGal-infected islet cells staining positive for beta-galactosidase. Transplant recipients became nomoglycemic within 48 hr after transplant, and, although beta-galactosidase expression decreased over time, it was detectable in the graft for up to 8 weeks. Despite the nanogram quantities of IL-4 or IL-10 produced/day from each graft equivalent in vitro, transduced and transplanted NOD islets failed to prevent disease recurrence. CONCLUSIONS: These results suggest that adenoviruses are efficient for at least medium term gene expression from islets in vivo, but neither IL-4 nor IL-10 alone can prevent autoimmune disease recurrence in NOD mice.     

Search for DNA repair inhibitors: selective binding of nucleic bases-acridine conjugates to a DNA duplex containing an abasic site

The abasic site is one of the most frequent DNA lesions generated by spontaneous or enzymatic cleavage of the N-glycosidic bond. The abasic site is also an intermediate in the nucleotide and base excision DNA repair. We examined molecules which recognize and cleave DNA at the abasic site with high efficiency. These molecules incorporate in their structure a nucleic base for abasic site recognition, an intercalator for DNA binding, and a polyamino linker for ionic interaction and DNA cleavage. Such compounds, by interfering with abasic sites in DNA, are also inhibitors of DNA repair. In order to better understand the parameters of the interaction, we carried out a UV thermal denaturation study of synthetic oligonucleotides containing the lesion both in the absence and in the presence of the drugs. A similar study was also carried out using the corresponding nonmodified oligonucleotide. The results indicate selective binding of the base-chain-intercalator conjugates to the abasic site containing oligonucleotides.     

Simultaneous determination of aortic valve area by the Gorlin formula and by transesophageal echocardiography under different transvalvular flow conditions. Evidence that anatomic aortic valve area does not change with variations in flow in aortic stenosis

OBJECTIVES: The purpose of this study was to determine the impact of changes in flow on aortic valve area (AVA) as measured by the Gorlin formula and transesophageal echocardiographic (TEE) planimetry. BACKGROUND: The meaning of flow-related changes in AVA calculations using the Gorlin formula in patients with aortic stenosis remains controversial. It has been suggested that flow dependence of the calculated area could be due to a true widening of the orifice as flow increases or to a disproportionate flow dependence of the formula itself. Alternatively, anatomic AVA can be measured by direct planimetry of the valve orifice with TEE. METHODS: Simultaneous measurement of the planimetered and Gorlin valve area was performed intraoperatively under different hemodynamic conditions in 11 patients. Left ventricular and ascending aortic pressures were measured simultaneously after transventricular and aortic punctures. Changes in flow were induced by dobutamine infusion. Using multiplane TEE, AVA was planimetered at the level of the leaflet tips in the short-axis view. RESULTS: Overall, cardiac output, stroke volume and transvalvular volume flow rate ranged from 2.5 to 7.3 liters/min, from 43 to 86 ml and from 102 to 306 ml/min, respectively. During dobutamine infusion, cardiac-output increased by 42% and mean aortic valve gradient by 54%. When minimal flow was compared with maximal flow, the Gorlin area varied from (mean +/- SD) 0.44 +/- 0.12 to 0.60 +/- 0.14 cm2 (p < 0.005). The mean change in Gorlin area under different flow rates was 36 +/- 32%. Despite these changes, there was no significant change in the planimetered area when minimal flow was compared with maximal flow. The mean difference in planimetered area under different flow rates was 0.002 +/- 0.01 cm2 (p = 0.86). CONCLUSIONS: By simultaneous determination of Gorlin formula and TEE planimetry valve areas, we showed that acute changes in transvalvular volume flow substantially altered valve area calculated by the Gorlin formula but did not result in significant alterations of the anatomic valve area in aortic stenosis. These results suggest that the flow-related variation in the Gorlin AVA is due to a disproportionate flow dependence of the formula itself and not a true change in valve area.     

Percutaneous angioplasty for infrainguinal graft-related stenoses

OBJECTIVE: To assess the success of percutaneous transluminal angioplasty (PTA) in treating infrainguinal graft-related stenoses. DESIGN: Retrospective analysis of stenoses undergoing PTA over 6 years. MATERIALS: Fifty-seven stenoses in 42 grafts. METHODS: Site, length and type of stenoses recorded. Follow-up till discharge, graft occlusion or death. RESULTS: PTA was successful in 48/57 stenoses in 36 grafts (G), with a poor result in seven. Further PTA was required in seven stenoses (7 G). One graft occluded at PTA and one stenosis was inaccessible. Overall graft (G) patency (median 13 months) was 82% (1 year patency 84%). Of 48 successful PTAs (37 G), 36 remained patent (28 G), eight (4 G) occluded and four were lost to follow-up (4 G). Fourteen of thirty-six stenoses which remained patent required further intervention (seven PTA, six jump grafts, one vein patch). The four occlusions were associated with small veins (two), multiple stenoses (one) and a PTFE graft which occluded 10 days following PTA. Of the seven PTAs with a poor angiographic result, five remained patent, three after further intervention. CONCLUSION: PTA is the best treatment for localised stenoses. Stenoses > 2 cm or multiple (three or more) stenoses are best treated surgically. Follow-up is essential, as 20% require further intervention.     

Correlation of interleukin-1 beta, interleukin-6, and periodontitis

In order to understand the role of IL-1 beta and IL-6 in the periodontal tissue destruction coincident to periodontitis, we assessed the levels of these two mediators in both the gingival tissue and the serum of patients with periodontal disease and of periodontally healthy subjects. In addition, production of IL-6 by six healthy human gingival fibroblast (HGF) strains in response to IL-1 beta was also investigated. The levels of IL-1 beta and IL-6 in gingival tissues and in serum were examined by ELISA. Both mediators were observed to increase in diseased tissues of patients with adult periodontitis, and there was a positively significant relationship between both mediators and clinical assessments of periodontal destruction. Moreover, a significant correlation was also noted between levels of IL-1 beta and IL-6 in gingival tissues of periodontitis patients (r = 0.4334, p < 0.01). However, there was no significant difference in the serum levels of IL-1 beta and IL-6 between periodontitis patients and periodontally healthy controls. In fibroblast cultures, confluent monolayers of HGF were incubated with recombinant human IL-1 beta for 48 h at 37 degrees C in 5% CO2 and air. At the end of the culture period, supernatants were collected and assayed for IL-6 activity by inducing proliferation in the IL-6-dependent hybridoma cell line 7TD1. A dose-dependent stimulatory effect of IL-1 beta on IL-6 production by HGF was noted, wherein 3 strains exhibited higher IL-6 activity than the other 3. These data indicate that the levels of IL-1 beta and IL-6 in gingival tissues are closely related to the severity of periodontal disease and that the IL-1 beta and IL-6 produced in gingival tissues may not reflect these two mediators levels in serum. Moreover, IL-1 beta responsiveness of HGF in IL-6 production depends on both the concentration of IL-1 beta and cells of individual subjects. Since HGF are present in periodontal lesion, it is possible that IL-6 secretion stimulated by exposure to inflammatory cell products such as IL-1 beta may participate in the destruction of periodontal tissue in periodontitis.     

An experimental study on inhibitory effect of Chinese medicine tai-bao on antisperm antibody

OBJECTIVE: To investigate whether Chinese medicine Tai-bao could inhibit antisperm antibody in experimental mice. METHODS: The experimental immunoinfertility mice were due to antisperm antibody induced by injection of human sperm membrane antigens. The experimental immuno-infertile mice used in the present study were divided into four groups including Tai-bao high dose group (46.8 g.kg-1.d-1), Tai-bao low dose group (31.2 g.kg-1.d-1), prednisone group and normal saline group. The enzyme linked immune sorbent assay (ELISA) and microcytotoxic assay were used for detection of antisperm antibody. The change of levels of antisperm antibody before and after treatment, pregnant rate, and the number of implantation were investigated in tested mice. RESULTS: The pregnant rates in normal saline group, prednisone group, Tai-bao high dose group and low dose were 38.89%, 47.06%, 70.00% and 75.00% respectively. The rate of pregnancy in Tai-bao low dose group was significantly higher as compared with normal saline group (P < 0.05). The rate of implantation in Tai-bao low dose group was significantly higher than that in prednisone group (P < 0.05). The results of detection of the cytotoxic antibody to sperm showed that cytotoxic percentages in Tai-bao high dose group (63.0 +/- 10.3%) and prednisone group (56.3 +/- 13.7%) were significantly lower (P < 0.05 and P < 0.01) than that in normal saline group (72.84 +/- 5.05%). CONCLUSION: Chinese medicine Tai-bao possesses regulatory effect on reproductive immune function, inhibitory effect on antisperm cytotoxic antibody, and promoting effect on pregnancy.     

Potentially predictive and manipulable blood serum correlates of aging in the healthy human male: progressive decreases in bioavailable testosterone, dehydroepiandrosterone sulfate, and the ratio of insulin-like growth factor 1 to growth hormone

A cross-sectional survey was made in 56 exceptionally healthy males, ranging in age from 20 to 84 years. Measurements were made of selected steroidal components and peptidic hormones in blood serum, and cognitive and physical tests were performed. Of those blood serum variables that gave highly significant negative correlations with age (r > -0.6), bioavailable testosterone (BT), dehydroepiandrosterone sulfate (DHEAS), and the ratio of insulin-like growth factor 1 (IGF-1) to growth hormone (GH) showed a stepwise pattern of age-related changes most closely resembling those of the age steps themselves. Of these, BT correlated best with significantly age-correlated cognitive and physical measures. Because DHEAS correlated well with BT and considerably less well than BT with the cognitive and physical measures, it seems likely that BT and/or substances to which BT gives rise in tissues play a more direct role in whatever processes are rate-limiting in the functions measured and that DHEAS relates more indirectly to these functions. The high correlation of IGF-1/GH with age, its relatively low correlation with BT, and the patterns of correlations of IGF-1/GH and BT with significantly age-correlated cognitive and physical measures suggest that the GH-IGF-1 axis and BT play independent roles in affecting these functions. Serial determinations made after oral ingestion of pregnenolone and data from the literature suggest there is interdependence of steroid metabolic systems with those operational in control of interrelations in the GH-IGF-1 axis. Longitudinal concurrent measurements of serum levels of BT, DHEAS, and IGF-1/GH together with detailed studies of their correlations with age-correlated functional measures may be useful in detecting early age-related dysregulations and may be helpful in devising ameliorative approaches.