Experimental and Clinical Studies of Biodegradable Polymeric Stents

The metallic stent has become the most common device to reduce acute occlusion and late restenosis after balloon angioplasty, but the long-term effects of metallic stents in human coronary arteries are still unknown. To overcome several problems of conventional stenting, there have been many attempts to manufacture stents made of biodegradable materials. Although some studies have noted various degrees of inflammatory responses after biodegradable stent implantation, stents made of poly-1-lactic acid (PLLA) showed high biocompatibility with minimal inflammatory response and neointimal formation in porcine coronary arteries. A clinical study of PLLA self-expanding stent implantation is underway in Japan. The initial and 6-month results are favorable and suggest the feasibility, safety, and efficacy of the PLLA biodegradable stent in humans. However, long-term follow-up with larger numbers of patients will be required to validate the long-term efficacy of PLLA stents.     

A Biodegradable Poly-l-lactic Acid Coronary Stent in the Porcine Coronary Artery

Although biocompatibility of biodegradable stents is controversial, stents made of high molecular weight poly- l -lactic acid (PLLA) are thought to be the most promising. We investigated the biocompatibility of PLLA stents histologically and angiographically in porcine coronary arteries. The Igaki-Tamai stent is made of PLLA monofilaments (molecular mass 183 kD) with a zigzag helical coil design. Fourteen PLLA stents in 6 pigs and 9 Palmaz-Schatz half stents in 9 pigs were implanted in 15 normocholesterolemic pigs. Stents were mounted on a delivery catheter, and were implanted percutaneously into coronary arteries. Coronary angiography was performed before and immediately after stenting, at 2 and 6 weeks in five PLLA pigs and nine Palmaz-Schatz pigs. Histological studies were performed in PLLA pigs: 2 pigs at 2 weeks, 3 pigs at 6 weeks, and 1 pig at 16 weeks with hematoxylin-eosin and elastica van Giesons stains. All PLLA stents were successfully delivered. No stent thrombosis was detected in either group. There were no significant differences in minimal lumen diameter (MLD) or percent diameter stenosis between the PLLA and Palmaz-Schatz stent groups immediately after implantation, or at 2 or 6 weeks after implantation. Histological studies at 2, 6, and 16 weeks revealed no inflammation and minimal neointimal coverage on the PLLA stent struts. The PLLA stent maintained its structure for up to 16 weeks. These results suggest sufficient biocompatibility and strength of PLLA biodegradable stents in porcine coronary arteries. Clinical trial is now underway to validate the safety and usefulness of PLLA stents in humans.     

Imaging characteristics of papillary renal cell carcinoma by computed tomography scan and magnetic resonance imaging

AIM: To analyse the differences in the patterns between clear and papillary renal cell carcinomas using magnetic resonance imaging (MRI) and dual-phase helical computed tomography (CT). METHODS: We examined seven patients with papillary renal cell carcinoma, and six with clear cell carcinoma. The highest attenuation value of tumors in the corticomedullary phase (CMP) and the excretory phase (EP) was measured using the observer-defined region of interest (ROI). MRI consisted of T1-weighted and T2-weighted spin-echo imaging. RESULTS: All five tumors except for one with papillary renal cell carcinoma showed homogenous hypointensity, but all six tumors with clear cell carcinoma showed heterogeneous hyperintensity on their T2-weighted images. In the CMP, the mean CT numbers of the papillary renal cell carcinomas were significantly lower than those of the clear cell carcinomas. The mean enhancement of the papillary renal cell carcinomas in the CMP and the EP was significantly lower than that of the clear renal cell carcinomas. The mean CT numbers of the clear cell carcinomas in the CMP were markedly increased from those on the unenhanced CT; those in the EP were decreased gradually. But the mean CT numbers of the papillary renal cell carcinomas in the EP were still slightly more increased than those in the CMP. The enhancement patterns of the papillary renal cell carcinomas in the CMP and the EP were homogenous, but those of the clear cell carcinomas were heterogeneous. CONCLUSIONS: We can speculate the differential diagnosis from clear to papillary renal cell carcinoma using MRI and dual-phase helical CT.     

A specific chromosome abnormality of t(4;12)(qll-12;pl3) in CD7+ acute leukaemia

Summary. Three cases of acute leukaemia with t(4;12) (qll-12;pl3) karyotypic abnormalities were analysed. They had the following common clinical and biological characteristics: (1) dysplasia of three haemopoietic lineages; (2) absent or low myeloperoxidase activity; and (3) retention of platelets in the peripheral blood and megakaryocytes in the bone marrow. There were increased numbers of basophils in the bone marrow and peripheral blood in two of the cases. In all, the blast cells displayed the unique immunophenotype CD7⁺CD13⁺CD34⁺HLA-DR⁺. The blasts analysed in one case expressed c-kit on the membrane surface. These findings suggest that the t(4:12) (qll-12:pl3) abnormality is associated with a particular type of acute leukaemia, one in which the morphology and immunophenotype suggest that the translocation may have occurred at an early stage of haemopoiesis.     

Approach for Chronic Total Occlusion With Intravascular Ultrasound–Guided Reverse Controlled Antegrade and Retrograde Tracking Technique: Single Center Experience

Background

Controlled antegrade and retrograde subintimal tracking (CART) or reverse CART techniques is the final step for percutaneous revascularization of coronary chronic total occlusion (CTO), but it still represents technical challenges and risk in interventional procedures.

Objectives

Our purpose was to utilize intravascular ultrasound (IVUS)‐guided reverse CART approach for percutaneous revascularization of CTO in our heart center, focusing on its safety, efficacy, and latest technical developments.

Methods

From November 2006 to November 2012, 49 patients with CTO failed to antegrade and/or retrograde percutaneous revascularization of CTO from true lumen to true lumen were enrolled in and underwent IVUS guided reverse CART approach.

Results

The mean J‐CTO score of cases was 2.5. IVUS guidance was successfully implemented in 95.9%; IVUS identified that 61.7% of retrograde wires were located at intimal space, and 59.5% of antegrade wires were located at subintimal space. A Corsair channel dilator was used in 77.6% of cases. The success rates of technique and procedure were 95.9% and 93.9%, respectively; the technical minor complications were observed in 10.2% of cases, without significant clinic outcomes; 2.0% of cases occurred with a major adverse cardiac event of non‐ST‐elevation myocardial infarction; and no case occurred with target vessel revascularization or death. The mean length of stent implanted in a single CTO vessel was 51.3 mm. No patient appeared with radiation dermatitis and contrast‐induced rise of creatinine.

Conclusions

IVUS guided reverse CART approach is effective and safe for percutaneous revascularization of complex CTO, with a high success and a low complication rate. It is feasible to develop this approach for percutaneous revascularization of complex CTO. However, suitable case selection and lately device handling by experienced operators are the crucial points of success. (J Interven Cardiol 2013;26:434‐443)

     

Delayed adrenal insufficiency long after unilateral adrenalectomy: Prolonged glucocorticoid therapy reduced reserved secretory capacity of cortisol

A 51-year-old woman with Cushing's syndrome underwent unilateral adrenalectomy for left adrenal adenoma. After 7 years of prednisolone treatment (with some interruptions), followed by 4 years of total withdrawal from prednisolone treatment, she presented with hypotension, weight loss, general fatigue, nausea, hyponatremia and hypoglycemia. These clinical features together with a low response in the rapid adrenocorticotropic hormone test led to the diagnosis of acute adrenal insufficiency. Relatively low serum adrenocorticotropic hormone levels in the face of increased demand for cortisol during adrenal crisis suggested a disordered hypothalamic-pituitary function, indicating secondary adrenal insufficiency. This patient demonstrated the etiology of acute adrenal insufficiency long after unilateral adrenalectomy in association with subsequent glucocorticoid therapy. A reduction in the reserved secretory capacity of cortisol after prolonged prednisolone treatment was considered to have induced secondary adrenal insufficiency, even after 4 years of total withdrawal from prednisolone.     

Renal tubular calcification in six nephrotic children with acute renal insufficiency

Summary: A review of 42 primary nephrotic children who underwent kidney biopsies found that six patients had calcification of the renal tubules (aged 2-9 years). These six patients showed significant increases in weight gain, blood pressure, urinary protein, serum urea nitrogen and urinary calcium/creatinine, and significant decreases in serum phosphate, % tubular reabsorption of phosphate and creatinine clearance as compared with 36 nephrotic patients without tubular calcification. Furthermore, these patients received high dose furosemide, and five of six patients received methylprednisolone pulse therapy to treat progressive renal dysfunction. the interval before the first kidney biopsy and after both the onset of the nephrotic syndrome, and the start of glucocorticoid therapy, including methylprednisolone pulse therapy and furosemide, ranged from 1 to 5 months excluding one patient (33 months). Although one patient received haemodialysis, renal insufficiency was resolved from 10 to 18 days after its onset. Glucocorticoid therapy, including methylprednisolone pulse therapy and high dose furosemide in primary nephrotic children with acute renal insufficiency, induced calcification of the renal tubules.     

Natural Products: Baicalin and Baicalein,Constituents of an Important Medicinal Plant,Inhibit Intracellular Ca2+ Elevation by Reducing Phospholipase C Activity in C6 Rat Glioma Cells

Glial cells have a role in maintaining the function of neural cells. This study was undertaken to clarify the effects of baicalin and baicalein, flavonoids isolated from an important medicinal plant Scutellariae Radix (the root of Scutellaria baicalensis Georgi), on glial cell function using C6 rat glioma cells. Baicalin and baicalein caused concentration-dependent inhibition of a histamine-induced increase in intracellular Ca²⁺ concentrations ([Ca²⁺]_i). The potency of baicalein was significantly greater than that of baicalin. The noradrenaline- and carbachol-induced increase in [Ca²⁺]_i was also inhibited by baicalein and both drugs inhibited histamine-induced accumulation of total [³H]inositol phosphates, consistent with their inhibition of the increase in [Ca²⁺]_i. These results suggest that baicalin and baicalein inhibit [Ca²⁺]_i elevation by reducing phospholipase C activity. The inhibitory effects of baicalin and baicalein on [Ca²⁺]_i elevation might be important in the interpretation of their pharmacological action on glial cells, such as inhibition of Ca²⁺-required enzyme phospholipase A₂.