Evaluation of Gianturco Coils for Closure of Large (≥3.5 mm) Patent Ductus Arteriosus

Objectives. This report evaluates the use of Gianturco coils to close large patent ductus arteriosus (PDAs) (≥3.5 mm) and describes transvenous delivery of 0.052-in. (0.132-cm) Gianturco coils.

Background. Coil closure of PDAs has become increasingly popular. However, the technique has significant limitations when used to close large PDAs. This report evaluates patient characteristics, PDA anatomy, hemodynamic variables, delivery technique and coil geometry to determine predictors of success.

Methods. Between January 1995 and January 1997, 16 of 118 patients undergoing catheterization for PDA closure were found to have large PDAs. Their median age and weight were 14 months (range 3 months to 43 years) and 8.5 kg (range 3.5 to 73), respectively. The mean PDA diameter was 4.3 mm (range 3.5 to 5.9). Closure of PDAs was attempted using transcatheter delivery of 0.038-in. (0.096-cm) and 0.052-in. coils. Differences in clinical, anatomic, hemodynamic and technical variables between successes and failures were compared.

Results. Eleven (69%) of 16 patients had successful closure of their PDA. Failures occurred only in patients <8 months of age with an indexed PDA diameter >7 mm/m and a pulmonary/systemic flow ratio ≥2.8:1. Use of 0.052-in. coils tended to reduce the incidence of embolization and the number of coils needed for closure.

Conclusions. Patients >8 months of age can have successful closure of large PDAs with currently available Gianturco coils. The 0.052-in. Gianturco coils can be used safely to close large PDAs in infants as small as 6 kg. Increased experience and improved coil design may improve closure rates of large PDAs in infants.     

"Z"型及网状食管支架置入后的病理学比较研究

目的探讨Z型及网状支架置入实验犬食管后局部的形态学变化特点.方法选择成年健康实验犬,均分为Z型组和网状组,采取自体阔筋膜移植固定法置入Z型或网状食管支架,分别于术后1,2,4,8 wk分批处死每组动物,取出置架部位的食管组织,进行大体、光镜、电镜分析,并比较两组的差异.结果自体阔筋膜移植固定法能有效地固定食管支架.支架术后1,2 wk局部食管粘膜炎症反应显著,成纤维细胞处于旺盛的增殖及分泌状态,有广泛肉芽组织形成及部分纤维化,食管组织开始向管腔内生长;术后4,8 wk增生组织已完全覆盖支架结构,并连接成片,管腔明显狭窄,局部大量的纤维结缔组织形成,炎症反应缓解.两组实验标本病理形态基本相似,仅"网状"组于术后1,2 wk炎症反应明显,粘膜广泛出现溃疡.结论支架术后食管组织主要表现为肉芽组织形成及纤维化,术后4,8 wk随着炎性反应的减弱,纤维化过程渐趋稳定.网状及Z型支架术后的病理过程基本一致,网状支架术后局部炎性反应显著加重.     

Effect of isoproterenol on the "early repolarization" syndrome.

A study has been carried out on a group of subjects with RS-T segment elevation, a normal variant of early repolarization. Following isoproterenol administration, the RS-T segment became isoelectric. In most cases this was accompanied by shorter QT and longer QTc intervals. The same effects were observed after physical exertion but not after atropine or amyl-nitrite. Propranolol administration exaggerated RS-T elevation. Considering the mechanism with which isoproterenol acts and some analogies with the electrocardiographic picture experimentally obtained by means of the unilateral stimulation of the stellate ganglions, the hypothesis is advanced that the normal variant of early repolarization is related to an enhanced activity of the right sympathetic nerves.     

Primary Prevention of Sudden Cardiac Death in Adults with Transposition of the Great Arteries: A Review of Implantable Cardioverter-Defibrillator Placement

Transposition of the great arteries encompasses a set of structural congenital cardiac lesions that has in common ventriculoarterial discordance. Primarily because of advances in medical and surgical care, an increasing number of children born with this anomaly are surviving into adulthood. Depending upon the subtype of lesion or the particular corrective surgery that the patient might have undergone, this group of adult congenital heart disease patients constitutes a relatively new population with unique medical sequelae. Among the more common and difficult to manage are cardiac arrhythmias and other sequelae that can lead to sudden cardiac death. To date, the question of whether implantable cardioverter-defibrillators should be placed in this cohort as a preventive measure to abort sudden death has largely gone unanswered. Therefore, we review the available literature surrounding this issue.     

Combination of "low-dose" ribavirin and interferon alfa-2a therapy followed by interferon alfa-2a monotherapy in chronic HCV-infected non-responders and relapsers after interferon alfa-2a monotherapy

AIM: To report on the efficacy, safety and tolerability of interferon alfa-2a combined with a low dose of ribavirin for relapsers and non-responders to alpha interferon monotherapy. METHODS: Thirty four chronic hepatitis C virus-infected non responders to interferon alfa-2a monotherapy (a course of at least 3 months treatment) and 13 relapsers to interferon alfa-2a monotherapy (a dose of 3 to 6 million units three times per week for at least 20 weeks but not more than 18 months) were treated with the same dose of interferon alfa-2a used before (3 to 6 million units three times per week) and ribavirin (10mg/kg daily) for 6 months. In complete responders, interferon alfa-2a was administered for further 6 months at the same dose used before as monotherapy. RESULTS: Seven (20.6%) of 34 non responders stopped the combined therapy due to adverse events, including two patients with histological and clinical Child A cirrhosis. In 17/27 (63%) non responders, the combined therapy was stopped after three months because of non response. Ten of the 27 non responders completed the 12 month treatment course. At a mean follow up of 28 months (16-37 months) after the treatment, 4/10 (15%) previous non responders still remained complete responders. All 13 previous relapsers completed the 12-month treatment course. At a mean follow up of 22 months (9-36 months) after treatment, 6/13 (46%) the previous relapsers were still sustained complete responders. CONCLUSION: Our treatment schedule of the combined therapy for 6 months of interferon Alfa-2a with a low dose of ribavirin (10mg/kg/day) followed by 6 months of interferon Alfa-2a monotherapy is able to induce a sustained complete response rate in 15% of non responders and 46% of relapsers with chronic hepatitis C virus related liver diseases comparable to those obtained with the standard doses of ribavirin 1000-1200 mg/day. Randomized prospective controlled trials using lower total amounts of ribavirin in combination with interferon should be performed.     

Phylogenetic profiles reveal evolutionary relationships within the "twilight zone" of sequence similarity

Inferring evolutionary relationships among highly divergent protein sequences is a daunting task. In particular, when pairwise sequence alignments between protein sequences fall <25% identity, the phylogenetic relationships among sequences cannot be estimated with statistical certainty. Here, we show that phylogenetic profiles generated with the Gestalt Domain Detection Algorithm–Basic Local Alignment Tool (GDDA-BLAST) are capable of deriving, ab initio, phylogenetic relationships for highly divergent proteins in a quantifiable and robust manner. Notably, the results from our computational case study of the highly divergent family of retroelements accord with previous estimates of their evolutionary relationships. Taken together, these data demonstrate that GDDA-BLAST provides an independent and powerful measure of evolutionary relationships that does not rely on potentially subjective sequence alignment. We demonstrate that evolutionary relationships can be measured with phylogenetic profiles, and therefore propose that these measurements can provide key insights into relationships among distantly related and/or rapidly evolving proteins.     

Papillary Fibroelastoma in Differential Diagnosis of Left Atrial Appendage Masses

Papillary fibroelastomas are benign tumors that usually originate from cardiac valves but may have other endocardial origins. We report the cases of 2 patients in whom left atrial appendage masses were initially diagnosed as thrombus. They were treated for embolic stroke and their symptoms resolved; however, their left atrial appendage masses did not regress. After surgery, histologic analysis of the resected masses revealed papillary fibroelastoma in both cases. We discuss the diagnostic and therapeutic dilemmas encountered in patients with papillary fibroelastomas and cardiac masses other than thrombus.     

Remodeling of ryanodine receptor complex causes "leaky" channels: a molecular mechanism for decreased exercise capacity

During exercise, defects in calcium (Ca²⁺) release have been proposed to impair muscle function. Here, we show that during exercise in mice and humans, the major Ca²⁺ release channel required for excitation–contraction coupling (ECC) in skeletal muscle, the ryanodine receptor (RyR1), is progressively PKA-hyperphosphorylated, S-nitrosylated, and depleted of the phosphodiesterase PDE4D3 and the RyR1 stabilizing subunit calstabin1 (FKBP12), resulting in “leaky” channels that cause decreased exercise tolerance in mice. Mice with skeletal muscle-specific calstabin1 deletion or PDE4D deficiency exhibited significantly impaired exercise capacity. A small molecule (S107) that prevents depletion of calstabin1 from the RyR1 complex improved force generation and exercise capacity, reduced Ca²⁺-dependent neutral protease calpain activity and plasma creatine kinase levels. Taken together, these data suggest a possible mechanism by which Ca²⁺ leak via calstabin1-depleted RyR1 channels leads to defective Ca²⁺ signaling, muscle damage, and impaired exercise capacity.     

Polyproline and the "spectroscopic ruler" revisited with single-molecule fluorescence

To determine whether Forster resonance energy transfer (FRET) measurements can provide quantitative distance information in single-molecule fluorescence experiments on polypeptides, we measured FRET efficiency distributions for donor and acceptor dyes attached to the ends of freely diffusing polyproline molecules of various lengths. The observed mean FRET efficiencies agree with those determined from ensemble lifetime measurements but differ considerably from the values expected from Forster theory, with polyproline treated as a rigid rod. At donor-acceptor distances much less than the Forster radius R(0), the observed efficiencies are lower than predicted, whereas at distances comparable to and greater than R(0), they are much higher. Two possible contributions to the former are incomplete orientational averaging during the donor lifetime and, because of the large size of the dyes, breakdown of the point-dipole approximation assumed in Forster theory. End-to-end distance distributions and correlation times obtained from Langevin molecular dynamics simulations suggest that the differences for the longer polyproline peptides can be explained by chain bending, which considerably shortens the donor-acceptor distances.     

Reoperation in an adult female with "right-sided" Hirschsprung's disease complicated by refractory hypertension and cough

Hirschsprung’s disease (HD) is an intestinal malformation caused by the innate absence of ganglion cells in the neural plexus of the colorectal wall, and is most common in male infants. It is rare in adult, and is usually left-sided. Herein we reported based on the CARE guidelines a case of a 47-year-old adult female suffering from “right-sided” HD complicated by refractory hypertension and cough. The patient with a history of cesarean section and with digestive unfitness (abdominal pain, distention, and constipation) only since 20 years old had recurrence of HD after initial surgery due to the incomplete removal of the HD-affected bowel based on a diagnosis of “chronic ileus”, leading to the relapse of the digestive symptoms and the emergence of some intractable circulatory and respiratory complications which could be hardly controlled by conservative treatment. During the long interval before coming to our department for help, she had been re-hospitalized for several times with various misdiagnoses and supplied merely with symptomatic treatment which could only achieve temporary symptomatic relief. At her admission to our department, the imaging examinations strongly indicated recurrent HD which was further supported by pathological examinations, and right hemi-colectomy was performed to remove the remnant aganglionic intestinal segment. Intraoperative and postoperative pathology supported the completeness of the definitive resection. Post-operation, the patient’s bowel motility significantly improved, and interestingly, the complications disappeared. For adult patients with long-term constipation combined with cough and hypertension, rare diseases like HD which requires definite surgery and which could be “right-sided” should not be overlooked. It is vital to diagnose and cure HD patients in childhood. Through the comparison of the two surgeries, it is noteworthy that for diagnosed HD, sufficient removal of the non-functional intestine confirmed by intraoperative pathology is essential.     

Thinking outside the "box"-the ultrasound contrast controversy

On October 10, 2007, the U.S. Food and Drug Administration (FDA) announced a new "black box" warning for the perflutren-containing ultrasound contrast agents, contraindicating their use in patients with acute coronary syndromes, acute myocardial infarction, and worsening or clinically unstable heart failure. These warnings ignore the proven efficacy of ultrasound contrast agents, the previously established safety of these compounds, the potential risks of alternative procedures, and the likely confounding effect of pseudocomplication. We suggest that the FDA Medical Imaging Division convene a panel of cardiologists experienced in a variety of imaging modalities to fully assess the adverse events that have been attributed to these agents and that any future FDA warnings acknowledge the possible influence of pseudocomplication, the proven efficacy of the modality in question for early and accurate diagnosis of cardiovascular disease, and the known and theoretical risks of alternative testing that may be necessary.     

Ground-glass, polyglucosan-like hepatocellular inclusions: A "new" diagnostic entity

BACKGROUND & AIMS: Ground-glass (GG) inclusions within hepatocytes are an important histopathologic marker of chronic hepatitis B virus (HBV) infection but may also be seen in Lafora's disease (myoclonus epilepsy), cyanamide alcohol aversion therapy, and type IV glycogenosis. We have noted a recent increased incidence of liver biopsy and postmortem specimens with GG inclusions associated with none of these etiologic factors. This study was undertaken to further delineate the clinical and liver pathologic features in such cases and their possible pathogenesis. METHODS: Ten cases with GG inclusions (8 biopsy, 2 postmortem) were examined by light and electron microscopy, and the patients' clinical records were reviewed. RESULTS: Light microscopy demonstrated pale pink, oval to crescentic intracytoplasmic inclusions with a predilection for periportal hepatocytes but sometimes present throughout the lobules. The inclusions were intensely positive on periodic acid-Schiff stain and digested with diastase. Transmission electron microscopy of two cases showed non-membrane-bound cytoplasmic collections of granules with mild-to-moderate electron density, consistent with abnormal glycogen granules. The patients included 7 transplant recipients (liver, hematopoietic stem cell), 3 with type 2 diabetes and a child on chronic parenteral nutrition for short bowel syndrome. Medications included immunosuppressive agents, antibiotics, and insulin. CONCLUSIONS: GG hepatocellular inclusions may be seen in individuals without HBV infection or other recognized etiologies, appear to be composed of abnormal glycogen and closely resemble polyglucosan bodies described in humans, animals, and experimental models. The possible pathogenetic roles of disturbed glycogen metabolism and polypharmacotherapy are stressed.     

Anomalous Origin of the Left Main Coronary Artery from the Right Coronary Artery with a Preaortic Course

We report the case of a 51-year-old woman who presented with stable angina pectoris and Canadian Cardiovascular Society class II functional capacity. An electrocardiogram during a treadmill exercise test showed substantial ST-segment depression in the inferolateral leads. Coronary angiograms revealed an anomalous origin of the left main coronary artery from the opposite sinus of Valsalva and an interarterial course between the ascending aorta and pulmonary artery. Although this phenomenon is dangerous, the patient refused further examination. We discuss the diagnosis and treatment of patients who have an anomalous origin of a coronary artery from the opposite sinus of Valsalva.