An Intrapleural Lung Prosthesis: Rationale, Design, and Testing

Abstract: Extracorporeal life support (ECLS or ECMO) is standard treatment for severe respiratory failure but poses many contraindications to future lung transplantation. The solution to this dilemma is the implantable gas exchange device (IGED) or artificial lung. Preliminary efforts to create such an artificial lung have been made since 1970 and include designs involving single devices, intravascular devices (i. e., IVOX), and combination heart–lung devices, Stringent requirements govern the design of such a device, the most important of which are high gas exchange efficiency, low resistance to blood flow, and size. This paper describes such a device. It incorporates large diameter inflow and outflow ports in close proximity and a low resistance wound hollow fiber core encapsulated in a compliant outer shell which conserves the work of the right ventricle. In a large animal model (adult sheep) this device was connected in line with the main pulmonary artery in series with the native lungs. This configuration has the advantages of using the lungs as an embolic filter, perfusing the lungs with fully oxygenated blood, and maintaining the integrity of the anatomy necessary for transplant. Laboratory experiments have run >8 h. Preliminary data show that the animals have remained hemodynamically stable while the devices have supported the animals completely by supplying 100% O₂ saturation with PO₂ values ranging from 250–350 mm Hg. Additionally, this model makes possible the study of respiratory failure without introducing other variables such as extracorporeal circuits or pumps. The other metabolic, endocrine, and reticuloendothelial functions of normal and injured lungs can now be studied more precisely by excluding these variables. Further studies are needed to evaluate this device in chronic (long–term implantation) experiments before clinical application.     

Rapid Administration of High-Dose Human Antibody Fab Fragments to Dogs: Pharmacokinetics and Toxicity

Rapid Administration of High-Dose Human Antibody Fab Fragmentsto Dogs: Pharmacokinetics and Toxicity. Keyler, D. E., Salerno,D. M., Murakami, M. M., Ruth, G., and Pentel, P. R. (1991).Fundam. Appl Toxicol 17, 83-91. The treatment of drug overdosewith drug-specific antibody fragments may require very highantibody doses. To address the feasibility of this therapy,we studied the pharmacokinetics and toxicity of high-dose humannonspecific Fab fragments in beagles. Three dogs received 5.3g/kg Fab iv over 1 hr. Because nephrotoxicity was observed,three subsequent dogs received 3.2 g/kg. The fraction of theFab dose excreted in urine (10 ± 6%%) was lower thanreported values for either high or low doses of Fab in otherspecies. The terminal serum elimination half-life (42 hr forthe higher and 48 hr for the lower dose) was also longer thanreported values for other species, due to lower renal and nonrenalFab clearance. Fab administration was tolerated without adversehemodynamic effects. One of three dogs at each dose developedtransient oliguria. All dogs developed a transient but markedincrease in the serum creatinine concentration. At 2 weeks creatinineclearance had returned to normal. Urinary protein and albuminexcretion at 2 weeks were within the normal range for dogs butwere increased over their baseline values. The histology ofall organs was normal at 3 weeks by light microscopy, and renalhistology by electron microscopy was also normal. The mechanismof Fab nephrotoxicity, not observed previously with high-doseFab in rats or lower doses of Fab in other species includingdogs, is not clear. These data suggest that further study ofthe potential toxicity of high-dose Fab, and its reversibility,is needed to assess the feasibility of treating drug overdosewith this antibody fragment The long terminal half-life of high-doseFab in the dog and its low renal clearance contrast with valuesobserved with lower doses of Fab in other species but wouldnot be expected to preclude the use of high-dose Fab for drugoverdose.     

The influence of HLA-matched sibling donor availability on treatment outcome for patients with AML: an analysis of the AML 8A study of the EORTC Leukaemia Cooperative Group and GIMEMA

To determine whether patients with a HLA-identical sibling donor have a better outcome than patients without a donor, an analysis on the basis of intention-to-treat principles was performed within the framework of the EORTC-GIMEMA randomized phase III AML 8A trial. Patients in complete remission (CR) received one intensive consolidation course. Patients with a histocompatible sibling donor were then allocated allogeneic bone marrow transplantation (alloBMT), the patients without a donor were randomized between autologous BMT (ABMT) and a second intensive consolidation (IC2). 831 patients <46 years old and alive >8 weeks from diagnosis were included. HLA typing was performed in 672 patients. AlloBMT was performed during CR1 in 180 (61%) out of 295 patients with a donor. Another 38 patients were allografted: five in resistant disease, 14 during relapse and 19 in CR2. ABMT was performed in 130 (34%) out of 377 patients without a donor in CR1, in six (2%) patients during relapse and in 38 (10%) patients during CR2. The disease-free survival (DFS) from CR for patients with a donor was significantly longer than for patients without a donor (46% v 33% at 6 years; P = 0.01, RR 0.78, 95% confidence interval 0.63–0.96). The overall survival from diagnosis for patients with a donor was longer, but not statistically significant, than for patients without a donor (48% v 40% at 6 years; logrank P = 0.24). When patients were stratified according to prognostic risk groups, the same trend in favour of patients with a donor was seen for survival duration and the DFS remained significantly longer for this group of patients.     

Primary Immunodeficiency Diseases in Latin America: The Second Report of the LAGID Registry

This is the second report on the continuing efforts of LAGID to increase the recognition and registration of patients with primary immunodeficiency diseases in 12 Latin American countries: Argentina, Brazil, Chile, Colombia, Costa Rica, Honduras, Mexico, Panama, Paraguay, Peru, Uruguay, and Venezuela. This report reveals that from a total of 3321 patients registered, the most common form of primary immunodeficiency disease was predominantly antibody deficiency (53.2%) with IgA deficiency reported as the most frequent phenotype. This category was followed by 22.6% other well-defined ID syndromes, 9.5% combined T- and B-cell inmunodeficiency, 8.6% phagocytic disorders, 3.3% diseases of immune dysregulation, and 2.8% complement deficiencies. All countries that participated in the first publication in 1998 reported an increase in registered primary immunodeficiency cases, ranging between 10 and 80%. A comparison of the estimated minimal incidence of X-linked agammaglobulinemia, chronic granulomatous disease, and severe combined immunodeficiency between the first report and the present one shows an increase in the reporting of these diseases in all countries. In this report, the estimated minimal incidence of chronic granulomatous disease was between 0.72 and 1.26 cases per 100,000 births in Argentina, Chile, Costa Rica, and Uruguay and the incidence of severe combined immunodeficiency was 1.28 and 3.79 per 100,000 births in Chile and Costa Rica, respectively. However, these diseases are underreported in other participating countries. In addition to a better diagnosis of primary immunodeficiency diseases, more work on improving the registration of patients by each participating country and by countries that have not yet joined LAGID is still needed. Latin American Group for Primary Immunodeficiency Diseases     

Microabrasion in tooth enamel discoloration defects: three cases with long-term follow-ups

Superficial irregularities and certain intrinsic stains on the dental enamel surfaces can be resolved by enamel microabrasion, however, treatment for such defects need to be confined to the outermost regions of the enamel surface. Dental bleaching and resin-based composite repair are also often useful for certain situations for tooth color corrections. This article presented and discussed the indications and limitations of enamel microabrasion treatment. Three case reports treated by enamel microabrasion were also presented after 11, 20 and 23 years of follow-ups.     

Influence of Age, Lead Axis, Frequency of Arrhythmic Episodes, and Atrial Dimensions on P Wave Triggered SAECG in Patients with Lone Paroxysmal Atrial Fibrillation

Signal-averaged P wave of 42 patients with lone paroxysmal atrial fibrillation (PAF) and 29 normal subjects (N) were recorded, using three orthogonal leads and analyzed in the time and frequency (entire P wave or a 100-ms segment ranging from 75 ms before to 25 ms after the end of P wave) domains. PAFs were divided into a group of 12 having ≥ 2 attacks a month (HF) and a group of 30 having ≤ 2 attacks a year (LF). Statistically significant differences were absent with regard to ages of PAF and N; ages of HF, LF, and N at the time of signal-averaged ECG; ages of HF and LF at the time of the first arrhythmic episode; and elapsed times from the first episode. Length of P wave and some frequency-domain parameters were found to be significantly correlated with age. PAF showed a significantly longer duration of P wave in the frontal plane using the time-domain analysis. Frequency analysis was found to be useful in evaluating the influence of attack frequency. HF showed significantly higher values of some frequency-domain parameters than LF and N, while the three groups did not differ for time-domain analysis. P wave duration and frequency content of the three orthogonal leads proved to be significantly different in PAF and N. Right and left atrial echocardiographic dimensions proved to be higher (even if within normal limits) in HF than in LF and N. Results suggest that frequency analysis should be performed on the entire P wave.