Process optimization with in situ technologies.

In situ technologies coupled with automated laboratory reaction systems are significantly improving the way we optimize and scale-up chemical processes. In situ analytical probes are ideal for the continuous monitoring of chemical and physical changes without disturbing the reaction environment, thereby eliminating questions of sample integrity. In manufacturing settings, these tools can offer advantages of increased efficiency, safety and cost savings. This review will discuss approaches to process development and highlight important recent contributions of in situ technologies and automated systems impacting process optimization for pharmaceutical development.

Transcatheter closure of atrial septal defect or patent foramen ovale with the buttoned device for prevention of recurrence of paradoxic embolism.

Transcatheter occlusion of patent foramina ovalia and atrial septal defects in 10 patients with presumptive paradoxic embolic stroke using the buttoned device appears to be encouraging, with safety and efficacy demonstrated during a follow-up of up to 60 months. Anticoagulation should be continued until complete disappearance of the right-to-left atrial shunt.

Follow-up results of transcatheter occlusion of atrial septal defects with buttoned device.

BACKGROUND: Feasibility, effectiveness and safety of transcatheter occlusion of secundum atrial septal defect (ASD) with buttoned device have been demonstrated. OBJECTIVES: To evaluate the follow-up results of the ASD with buttoned device method to assess its long term efficacy and safety. PATIENTS AND METHODS: Patient age at device implantation ranged from seven months to 51 years and weight ranged from 3.6 to 105 kg. Successful implantation of the device was accomplished in 20 of 22 consecutive patients (91%) seen during a 33-month period ending August 1992. Patients were divided into three groups based on the type of shunt across the ASD: group I (n = 14)--left-to-right shunt; group II (n = 5)--presumed paradoxical embolism; and group III (n = 1)--right-to-left shunt. These 20 patients were followed for 29 +/- 11 months, range 16 to 52 months. Follow-up included clinical evaluation, chest x-ray and echo-Doppler studies, and was performed two weeks, and three, six and 12 months after occlusion and yearly thereafter. Most patients received 5 to 10 mg/kg/day acetylsalicylic acid for 12 weeks following the device implantation. RESULTS: In 14 left-to-right shunt ASD closures, the right ventricular size diminished from 2.3 +/- 0.6 to 1.7 +/- 0.3 cm immediately after closure (P < 0.01) and remained decreased (1.6 +/- 0.46 cm) at last follow-up. Paradoxical/flat septal motion was present in 11 of 14 patients (79%) before closure while such an abnormal septal motion was not present in any at follow-up. Small to trivial left-to-right shunts across the implanted device were seen in six of 14 patients (43%) immediately after closure while trivial shunts were present in three of 14 (21%) at follow-up. Small shunts became trivial and trivial shunts disappeared. None of the patients had any clinical signs of ASD and none required surgical intervention during the follow-up period. None of the five patients with cerebrovascular accident (CVA)/paradoxical embolism had recurrence of CVA. Repeat transesophageal contrast echocardiographic study with Valsalva revealed minimal right-to-left shunt in two of five patients (40%) initially, which disappeared at follow-up. The single patient with CVA secondary to atrial right-to-left shunt following previous tetralogy repair had a transient ischemic episode four months after closure and underwent surgery at the discretion of the primary cardiologist. There were no wire fractures on follow-up x-rays. None developed endocarditis. CONCLUSIONS: These data indicate that effective ASD occlusion can be accomplished in left-to-right shunt and paradoxical embolism patients. Modification of the device to position the square-shaped patch on the right atrial side may be necessary to prevent CVA in patients with right-to-left shunts.

Left ventricular dual-energy digital subtraction angiography: a motion immune digital subtraction technique.

Digital subtraction angiography (DSA) allows quantitative analysis of ventricular function via densitometric and parametric imaging techniques. However, DSA is limited by the artifacts in temporal subtraction images that result from patient and cardiac motion. Dual-energy subtraction imaging is insensitive to motion. This study evaluated the initial application of dual-energy subtraction in cardiac patients. The image quality of dual-energy subtraction left ventriculograms obtained from a pulmonary artery injection of contrast was assessed in 13 patients, ranging in weight from 54 to 100 kg. The dual-energy images were compared with left ventricular images obtained using standard left ventricular injection cine angiography. End-systolic and end-diastolic ventricular volumes calculated from the cine (C) and dual-energy (DE) images using the Area-Length method were compared. The resulting regression line was DE = 0.98 C+ 7.0 ml, and the r value was 0.987. Dual-energy subtraction provided good left ventricular visualization, free from misregistration artifacts, even during patient motion.