Total percutaneous correction of a tetralogy of Fallot variant with dominant pulmonary valve stenosis.

OBJECTIVE: To study the feasibility, efficacy, and safety of total percutaneous correction of a tetralogy of Fallot variant with dominant pulmonary valve stenosis. DESIGN: Percutaneous correction of a variant of tetralogy of Fallot with dominant pulmonary valve stenosis, on the basis that there are transcatheter methods for the correction of malalignment-type ventricular septal defect (VSD) (transcatheter patch) and valvar pulmonary stenosis (balloon valvoplasty). PATIENTS: Two patients with tetralogy of Fallot, 4 and 7 years old, were admitted for percutaneous correction. Their aortic saturations were 72% and 88%. Both had severe right ventricular outflow obstruction with dominant valvar pulmonary stenosis with total gradients of 120 and 70 mm Hg. Large malalignment subaortic VSDs, 14 and 16 mm in diameter, were present. The first patient had a previous percutaneous correction of a small atrial septal defect and an aortopulmonary collateral. INTERVENTIONS: Balloon valvoplasty was first performed, followed by balloon test occlusion of the VSD and double balloon patch occlusion. Forty eight hours after implantation the supporting balloons were extracted, releasing the patches. RESULTS: Both patients became acyanotic with oxygen saturations of 96%. There was mild residual infundibular stenosis with 40 and 30 mm Hg gradients. Both VSDs were effectively occluded with only trivial residual shunts. One patient developed mild haemolysis, which resolved spontaneously in a few days. Both patients were doing well at six and 12 months' follow up visits. CONCLUSIONS: Total percutaneous correction of the tetralogy of Fallot variants with dominant pulmonary valve stenosis is feasible and successful. Larger clinical trials are required to further assess effectiveness and safety.

Conformational properties of DNA after exposure to gamma rays and neutrons.

DNA aqueous solutions were irradiated with 0-40 Gy of 60Co gamma rays and 0-1.5 Gy of (Pu-Be) neutrons. Thermal transition spectrophotometry (TTS) was used to trace the changes in the DNA conformation at the above doses. Previous results using the perturbed angular correlation (PAC) method were used to complement to the current analysis. The TTS and PAC methods are two different approaches to the study of the effects of radiation on DNA. Both showed that neutrons are more effective than gamma rays in inducing DNA damage. The TTS method showed that neutrons are 11 +/- 5 times more efficient than gamma rays, while the PAC method had shown this value to be 34 +/- 4. From the current study we deduced that the radiation damage to DNA is not a spontaneous effect but rather is an ensemble of damaging events that occur asynchronously. Any single method selected for the study of such damages can concentrate on only a part of the damage, leading to over- or underestimation of the relative effectiveness of the neutrons.

Advances in transcatheter patch occlusion of heart defects.

UNLABELLED: The transcatheter patch device consists of the following components: a sleeve type polyurethane patch, a double balloon support catheter and a retrieval thread. It has been applied in a variety of heart defects, including various types of atrial septal defects, ventricular septal defects and patent ductus arteriosus. New advances include an accelerated release time for many applications and better immobilization. Using accelerated fibrin formation principles, transcatheter path release time has been decreased to less than 24 hours for patient ductus arteriosus and some ventricular septal defects; in contrast 48 hours are required for patch release in large atrial septal defects. The device is also unlikely to move away from the septum using the new immobilization methods. Since the patch is inflatable, only three sizes are required for the occlusion of all defect types and sizes. CONCLUSION: In conclusion the transcatheter patch is applicable in a variety of heart defects; the procedure is safer and faster, becoming outpatient, for many applications. Furthermore, it is cost effective.

Changes in DNA flexibility after irradiation with gamma rays and neutrons studied with the perturbed angular correlation method.

Neutron and gamma irradiation of buffered solutions of calf thymus DNA resulted in changes in the dynamics of the macromolecule. In the low-dose region (0.8-10 cGy of 239Pu-Be neutrons and 0.34-3 Gy of 60Co gamma rays), the flexibility of DNA decreased as indicated by slower rotation of the molecules. Neutrons appeared to be approximately 35 times more effective than 60Co gamma rays. The rotational correlation time, tau C, was measured using the perturbed angular correlation (PAC) method. Its variation appears to follow a linear-exponential behavior. An attempt is made to formulate this behavior as a function of the energy deposited on the macromolecule (radiation dose), the average threshold energy (dose) required to form new lesions, and the available population of intact DNA sites.

The Role of the 'Sideris' Devices in the Occlusion of Ventricular Septal Defects.

Transcatheter ventricular septal defect (VSD) occlusion was performed in 55 patients using two disk devices (the buttoned device transvenously and the self-adjustable device transarterially) and wireless devices (transcatheter patch and balloon detachable devices) transvenously. Most of the VSDs were perimembranous (45) and the rest congenital muscular (five) and postinfarction (five). All patients had effective occlusion of their VSDs; two early buttoned device cases had aortic interference and were removed surgically. All the used devices were successful in occluding VSDs; the transvenous approach was lengthier. The transarterial approach was the easiest, although not feasible in all cases. The transcatheter patch appears the most promising for perimembranous defects because of the safety features and minimal rim requirements.

Platypnea-orthodeoxia: management by transcatheter buttoned device implantation.

Dyspnea and arterial desaturation on upright position in elderly subjects is described as platypnea-orthodeoxia syndrome (POS) and in some patients it is due to right-to-left shunt across the atrial septal defect (ASD)/patent foramen ovale (PFO). Surgical closure of ASD/PFO has been the only available treatment option. Buttoned device has been used for occlusion of ostium secundum ASD, PFO associated with presumed paradoxical embolism and cerebrovascular accidents and ASD/PFO in association with other congenital heart defects causing right-to-left shunt. The objective of this article is to describe the use of buttoned device in effectively occluding ASD/PFO to relieve hypoxemia of POS. During a 4-year period ending January 2000, 10 patients, ages 71 +/- 9 (range 60-83) years with POS underwent buttoned device closure of their ASD/PFO. Echocardiographic and balloon-stretched atrial defect sizes were 8 +/- 3 mm and 12 +/- 3 mm, respectively. The ASD/PFO were occluded with devices ranging in size from 25 to 40 mm delivered via 9 French, long, blue Cook sheaths; eight had an additional 25- or 35-mm occluder placed on the right atrial side. The oxygen saturation increased (P < 0.001) from 76 +/- 7% (range 69-86%) to 95 +/- 2% (range 92-98%). No complications were encountered. Relief of symptoms was seen in all patients. Follow-up of 1-36 months (median 12 months) revealed persistent improvement of symptoms. Buttoned device occlusion of ASD/PFO to relieve hypoxemia of POS is feasible, safe, and effective and is an excellent alternative to surgery. Cathet Cardiovasc Intervent 2001;54:77-82.

Probing irradiated DNA with the perturbed angular correlation method.

The technique of perturbed angular correlations of gamma rays has been used to study the effects of radiation on DNA molecules. The samples are buffered solutions of calf thymus DNA exposed to various doses (0-80 Gy) of gamma rays. Indium-111 is used as a probe. Rotational correlation times, tau(c), a parameter measuring the flexibility of a macromolecule, are obtained that show a dependence on radiation dose.

From disk devices to transcatheter patches: the evolution of wireless heart defect occlusion.

Since 1988, we have been using double-disk devices with several device generations and improving results. Our current disk device, "The ButtonSeal Centering on Demand Device," is a multipurpose device made of stainless steel and polyurethane. It has shown high occlusion rates and no significant complications in atrial septal defects (ASDs) up to 30 mm in diameter. It can be used according to the ASD anatomy both in large, single defects (centering) and in multiple fenestrations (noncentering). The ButtonSeal shares the same limitations as other disk devices, namely, the possibility of wire-related problems and the need for significant septal rim. The development of wireless balloon-delivered devices and patches addresses these problems and limitations. Both detachable balloon devices and patches were used experimentally in animals and in feasibility studies in humans. The results showed good occlusion rates and lack of wire-related complications. Both methods required a minimal rim and occluded more defects than the disk devices. The transcatheter patch method was safer and had only one disadvantage, which was the need for 48-hour balloon support.

The Sideris buttoned devices for transcatheter closure of patent ductus arteriosus.

This article reviews the experience in the last decade with Sideris buttoned devices for occlusion of patent ductus arteriosus (PDA). The devices used were the regular buttoned device, the infant buttoned device, the device with the folding plug, and the wireless device. The buttoned devices were implanted transvenously and introduced through 7Fr-8Fr long sheaths for PDAs up to 12 mm; wireless devices required 9Fr-11Fr sheaths for PDAs up to 22 mm. All different shapes of ductus were occluded. The records of 356 patients in the international and Food and Drug Administration (FDA) supervised United States (US) clinical trials were reviewed. Despite excellent long-term full occlusion rates and the absence of significant complications with the regular buttoned device, modifications were necessary to improve the full occlusion rates in 24 hours. The 24-hour rates improved from 60% with the regular device to 85% with the folding plug device. Most residual shunts disappeared on long-term follow-up without significant complications. Wireless devices were developed for very large PDAs and have excellent occlusion rates. The buttoned device with the incorporated folding plug and the wireless devices are currently under clinical trial. The safety record of the new devices needs to be established with larger clinical trials.

Centering-on-demand buttoned device: its role in transcatheter occlusion of atrial septal defects.

Since the initial design and description of the buttoned device, it has undergone a number of design changes. Introduction of radiopacity in the knot (button) made it easier to visualize and document that buttoning has indeed occurred. Introduction of two buttons has markedly decreased the unbuttoning rate with potential for eliminating it. A centering mechanism was then incorporated into the device, which allowed closure of larger defects and use of smaller-sized devices. For some unknown reason, unbuttoning rate no longer occurs since the introduction of this device. The centering-on-demand (COD) device also appears to have increased the effective occlusion rates. At the present time, however, no long-term follow-up data are available to assess the long-term efficacy of the new device. Experience in a larger number of patients and evaluation of follow-up data are necessary to confirm the safety and efficacy observed in the small cohort reported in this review.

Transcatheter atrial septal defect occlusion in piglets by balloon detachable devices.

Detachable balloon devices were applied in the occlusion of experimental ASDs in 20 piglets. The detachable balloons were made from Latex; the occluder balloon was placed on the left atrial side and required a floppy disk and counter-occluder(s) support from the right atrial side (17 experiments), or a second detachable balloon from the right side (3 experiments). Full occlusion was noticed in all cases. There was one device embolization in the descending aorta (device with a regular floppy disk and no counter-occluder). The device was covered by tissue in 3 to 4 weeks with the balloon flat on the septum in approximately 2 months; it required minimal rim and no wires in the left atrium. The double balloon model was wireless. The balloon detachable device was found effective and safe in the occlusion of experimental ASDs in piglets.

Results of transvenous occlusion of secundum atrial septal defects with the fourth generation buttoned device: comparison with first, second and third generation devices. International Buttoned Device Trial Group.

OBJECTIVES: The purpose of this study was to assess safety and effectiveness of the fourth generation buttoned device in dosing atrial septal defects (ASDs) and to test the hypothesis that introduction of double button reduces unbuttoning rate without reducing effectiveness. BACKGROUND: Because of the high unbuttoning rate (7.2%) with first, second and third generation buttoned devices, the device was modified (fourth generation) so that there were two radiopaque spring buttons 4 mm apart on the button loop attached to the occluder. METHODS: During a four-year period ending in September 1997, 423 patients, ages 1.5 to 80 years (median 16 years), underwent closure of ASD at 40 medical centers around the world. RESULTS: The ASD size varied between 5 and 30 mm (median 17 mm). The device size varied between 25 and 60 mm. Unbuttoning occurred in 4 (0.9%) of 423 patients. Effective occlusion, defined as no (n = 343) or trivial (n = 34) residual shunt on echo-Doppler studies performed within 24 h of the procedure, was demonstrated in 377 patients (90%). Thus, the unbuttoning rate (0.9 vs. 7.2%) decreased (p<0.01) while effective occlusion rate (90 vs. 92%) remained unchanged (p>0.1) with this device, compared with earlier generation devices. During follow-up from one month to five years (23+/-15 months), 21 (5%) of 417 patients required surgical (n = 12) or transcatheter (n = 9) reintervention, mostly to treat significant residual shunt. In the remaining patients there was gradual reduction and disappearance of the residual shunt. No wire integrity problems were observed. CONCLUSIONS: These data suggest that the fourth generation buttoned device is as effective as earlier generation devices, but without significant unbuttoning. Follow-up results remained good, with a reintervention-free rate of 89% at five years.

Diversity of peripheral blood mononuclear cells as revealed by a novel multiple microgel "comet assay".

Multiple microgel comet assay (MMCA) is a metho-dological adaptation of the single-cell gel electrophoresis assay in which we have introduced the use of standard agarose plug molds in an attempt to improve and expand the applications of the assay. We focused on the study of the heterogeneity of peripheral blood mononuclear cells (PBMC) at the level of the basal single-strand breakage and the DNA damage induction caused by ionizing radiation. Differences among subpopulations were also investigated at the level of chromatin organization and methylation after NotI digestion of microgel-embedded cells. In parallel experiments, the NotI-digested nucleoids were also analyzed with the use of pulsed-field gel electrophoresis (PFGE) and the DNA migration patterns were compared with the corresponding patterns from the MMCA. Significant heterogeneity in the distribution of the oxidative DNA damage, as well as intracellular variations in the NotI digestion patterns were observed in the cell population of PBMC. The combined use of both the comet assay and PFGE provides a useful model for analysis of variation in DNA damage in individual cells as well as information on size of DNA fragments.

Effects of radical scavengers on radiation-induced DNA double strand breaks.

PURPOSE: To investigate possible effects of Tris and phenol on the dynamic properties of gamma-irradiated DNA molecules in addition to their well known scavenging capacity. MATERIALS AND METHODS: Native and fragmented calf thymus DNA molecules were exposed to various doses of 60Co gamma-rays at approximately 4.5Gy/min. Using thermal transition spectrophotometry, pulsed field gel electrophoresis and standard agarose gel electrophoresis, the effects of Tris, phenol and NaCl on the double helix to single coil thermal transition temperature, Tm, and the yield of the double-strand breaks (Gdsb) of the irradiated DNA molecules have been studied. RESULTS: DNA molecules exposed to gamma-rays showed a decreased Tm and a corresponding increase of the Gdsb yield. Tris, as well as phenol, exhibited a strong protection against preventing these radiation-induced alterations. In addition, both substances strongly affected the thermal stability of the non-irradiated DNA samples. These results, compared with data obtained by NaCl and its effects on DNA thermostability and Gdsb, revealed that in the presence of both scavengers the observed dsb decrease was correlated to an increased molecular stability of DNA. CONCLUSIONS: This work suggests that the total protective effect of Tris and phenol against radiation-induced dsb is mainly attributed to their well-known radical scavenging properties, while relatively minor protective effects arise from their contribution to an increased molecular stability of DNA.

Alpha-particle-induced changes in the stability and size of DNA.

The effect of alpha-particle radiation on the thermal stability and size of calf thymus DNA molecules in deoxygenated aqueous solutions was investigated by thermal transition spectrophotometry, pulsed-field gel electrophoresis, and standard agarose gel electrophoresis. The thermal transition of DNA from helix to coil was studied through analysis of the UV A(260) absorbance. The results obtained for alpha particles of mean LET of 128 keV microm(-1) reveal a dual dose response: a tendency for thermal stability of the DNA helix at "low" doses, followed by an increasing instability at higher doses. The same phenomenon was observed for the mean molecular weight of DNA molecules exposed to alpha particles. The results reported here for alpha particles in the low-dose region of 0-16 Gy are consistent with our previous hypothesis of inter- and intramolecular interactions of a covalent character in gamma-irradiated DNA molecules in the dose region of 0-4 Gy.

Low doses of alpha- and gamma-radiation enhance DNA thermal stability.

Isolated calf thymus DNA in buffered solutions has been exposed to 0-150 Gy of alpha- and gamma-radiation. The effects of alpha- and gamma-radiation on the thermal stability and electrophoretic mobility of the DNA molecules have been studied by UV spectroscopic 'melting' and Pulsed Field Gel Electrophoresis (PFGE), respectively. The observed thermal denaturation parameters were fitted to the energy propagation descriptive model. The experimental results for the samples exposed to relatively low (low) doses indicate an increased thermal stability and a reduced mobility over that of the controls. The expected overall degradation of the DNA molecules was confirmed for the samples exposed to high doses. Our results are in good agreement with the predictions of the energy propagation model, which now is also tested in the low dose region and for an additional type of ionising radiation (alpha-particles). Our findings are consistent with conformational changes at low doses resulting in a DNA form characterised by localised alterations, which affect the energy flow along the DNA molecule.

Follow-up results of transvenous occlusion of patent ductus arteriosus with the buttoned device.

OBJECTIVES: The purpose of this presentation is to document results of buttoned device (BD) occlusion of patent ductus arteriosus (PDA) in a large number of patients with particular emphasis on long-term follow-up in an attempt to provide evidence for feasibility, safety and effectiveness of this method of PDA closure. BACKGROUND: Immediate and short-term results of BD occlusion of PDA have been documented in a limited number of children. METHODS: During a six-year period ending August 1996, transcatheter BD closure of PDA was attempted in 284 patients, ages 0.3 to 92 years (median 7) under a protocol approved by the local institutional review boards and FDA with an investigational device exemption in U.S. cases. RESULTS: The PDAs measured 1 to 15 mm (median 4) at the narrowest diameter; 20 were larger than 8 mm and 10 larger than 10 mm. They were occluded with devices measuring from 15 to 35 mm delivered via 7F (N = 140) or 8F (N = 144) sheaths. Successful implantation of the device was accomplished in 278 (98%) of 284 patients. The Qp:Qs decreased from 1.8+/-0.6 (mean+/-SD) to 1.09+/-0.19 (p < 0.001). Effective occlusion defined as no (N = 167 [60%]) or trivial (N = 79 [28%]) residual shunt was achieved in 246 (88%) patients. All types of PDAs, irrespective of the shape (conical, tubular or short), size (small or large) or length (short or long) of the PDA and previously implanted Rashkind devices, could be occluded. Follow-up data, 1 to 60 months (median 24) after device implantation, were available in 234 (84%) patients. Seven (3%) patients required reintervention to treat residual shunt with (N = 2) or without (N = 5) hemolysis. Actuarial reintervention-free rates were 95% at 1 and 5 years. There was gradual reduction of actuarial residual shunts and were 40%, 28%, 21%, 14%, 11%, 10%, 6% and 0% respectively at 1 day, 1, 6, 12, 24, 36, 48 and 60 months after device implantation. Incorporation of folding plug over the button loop in 10 additional patients produced immediate and complete occlusion of PDA. CONCLUSIONS: This large multiinstitutional experience confirms the feasibility, safety and effectiveness of buttoned device closure of PDAs. All types of PDAs irrespective of the shape, length and diameter can be effectively occluded. Incorporation of folding plug over the button loop produces complete PDA occlusion at the time of device implantation.

Studies on the interaction of diflunisal ion with cyclodextrins using ion-selective electrode potentiometry.

The interaction of diflunisal ion (DF) with beta-cyclodextrin (betaCD), gamma-cyclodextrin (gammaCD), and hydroxypropyl-beta-cyclodextrin (HPbetaCD) was studied in phosphate buffer, pH 7.4, at 5-37 degrees C and various CD concentrations using a home-made diflunisal ion-selective electrode. Typical direct binding plots and Scatchard plots were obtained with HPbetaCD. The Scatchard model for one class of binding sites was used for the estimation of binding parameters for the DF/HPbetaCD interaction. The estimates for n (number of binding sites per CD molecule) were in all cases very close to unity, indicating 1:1 complexation. The association constant (K) estimates decrease with increasing temperature. Sigmoidal direct binding plots and concave-downwards Scatchard plots were obtained with various betaCD or gammaCD concentrations. The Hill model was used for the estimation of the binding parameters for the DF/betaCD and DF/gammaCD interactions. Both the Hill coefficients and the binding constants were markedly dependent on the CD concentration. These findings indicate the cooperative character of DF/betaCD and DF/gammaCD interactions. The free energy change, DeltaG, and the thermodynamic parameters, DeltaH and DeltaS, were estimated for each of the interactions studied using the Van't Hoff equation.