CORRELATION BETWEEN AGE AND PLASMA LEVEL/DOSAGE RATIO FOR PHENOBARBITAL IN INFANTS AND CHILDREN

Abstract. 123 plasma concentration measurements of phenobarbital were obtained from 82 children (2 months - 6 1/2 years old) at steady-state conditions. The plasma level/dosage ratio has been found to have a highly significant correlation with the age of the patient both for dosage in mg/kg and in mg/m². The ratio increases with the increase in the age of the patient at a rate which is greater for dosages expressed on the basis of body weight. Moreover, at least for body weight related dosages, this increase is relatively high in the first year of life, becoming less marked after. Practical indications are given about the required dosage of phenobarbital in different groups of ages from 2 months up to 6 1/2 years. It is recommended however to regularly measure the plasma level of the drug in infants and children treated for long periods of time.     

Pathogenicity of the intercellular antibodies of pemphigus and their periodic removal from the circulation by plasmapheresis

The authors are convinced that the intercellular antibodies of pemphigus are pathogenic. Consequently periodic plasmapheresis in two patients with pemphigus has been performed to remove the antibodies from the circulation. After larger plasma-exchanges there was a decrease of the antibody titre and a parallel improvement of the clinical condition.     

Synthesis and activity of the glutathione analogue γ-(L-γ-azaglutamyl)-L-cysteinyl-glycine

The backbone-modified glutathione analogue γ-(L-γ-azaglutamyl)-L-cysteinyl-glycine 7, characterized by the presence of a NHCONH urea linkage deriving from the replacement of the native Glu γ-CH₂ with the aza (NH) group, was synthesized and fully characterized by FAB-MS, ¹H- and ¹³C-NMR. Potential of 7 and its oxidized form 6 as γ-glutamyltransferase inhibitors was investigated. Both compounds 7 and 6 were found to be competitive inhibitors of hog kidney y-glutamyltransferase (EC 2.3.2.2.) by binding at the donor site: the reduced analogue is a more efficient inhibitor than glutathione of the γ-glutamyl transfer reaction. Inhibition at the acceptor site, which is also present, appears to be more complex. In particular, un-competitive inhibition is observed for compound 7. The results indicate that γ-azapeptides of type 7 may represent interesting targets in the search for stable inhibitors of γ-glutamyltransferases. © Munksgaard 1995.     

UNUSUAL COMBINED IMMUNODEFICIENCY SYNDROME EXHIBITING KAPPA-IGD PARAPROTEINEMIA,RESIDUAL GUT-IMMUNITY AND GRAFT-VERSUS-HOST REACTION AFTER PLASMA INFUSION1

A 12-year-old suffering from a lymphopenic severe CID with an unusual protracted clinical course is presented. His gut-associated lympho-epithelial system was apparently normal, in contrast to the IgA deficiency in other external fluids. In addition, an elevated kappa-IgD was detected in his serum. Fresh plasma infusions from unrelated donors induced an accidental engraftment with a moderate non-fatal GvHR.     

Immune complex glomerulonephritis in experimental kala-azar

In the present work we demonstrate that hamsters infected with L. donovani eliminate large quantities of immunoglobulins in the urine. This alteration is clearly a consequence of a conspicuous immune complex glomerulonephritis readily detectable 7 days after the beginning of infection. L. donovani antigens and hamsters immunoglobulins (Igs) were revealed as granular deposits in the mesangial areas and contiguous loops of the glomeruli. Histopathological alterations such as focal mesangial proliferation with progression to diffuse proliferation were observed in the first 3 weeks of infection. From day 35 onwards, all diseased animals presented large deposits of amyloid material of predominantly glomerular localization. In consonance with these alterations, Igs were detected in the urine by day 21 of infection and their concentration increased substantially with the progression of disease. In contrast, serum Igs increased until day 21, when their concentration dropped steadily.     

Radiofrequency Ablation of Pediatric AV Nodal Reentrant Tachycardia during the Ice Age: A Single Center Experience in the Cryoablation Era

Background: Radiofrequency catheter ablation of atrioventricular nodal reentrant tachycardia (AVNRT) has proven to be an effective therapy in the pediatric population. However, concerns of inadvertent permanent AV nodal block have resulted in many pediatric programs adopting cryoablation as their primary ablation approach for AVNRT.
Methods: A retrospective analysis of the results of pediatric radiofrequency catheter ablation at a single institution over the most recent 5 years (January 2004 through December 2008) was performed. Acute, intermediate, and long-term success, along with the incidence of AV block, were determined.
Results: There were 65 patients with a mean age of 12.1 ± 5.2 years and weight of 46.5 ± 17.3 kg who underwent radiofrequency catheter ablation for AVNRT. There was 100% acute success with no recurrences at a mean follow up of 32.5 months. Although two patients had a brief second-degree AV block, there was no permanent AV block of any degree.
Conclusions: The safety and efficacy of radiofrequency catheter ablation for pediatric AVNRT demonstrated in this study support its continued application and should not be abandoned as a method of treatment. (PACE 2010; 6–10)     

Second Messenger Function of Arachidonic Acid Lipoxygenation Products in Human Natural Killer Cell Lysis?

Human natural killer (NK) cells were tested in the presence of several fatty acid oxygenase inhibitors such as nordihydroguaiaretic acid (NDGA), 5,8,11,14-eicosatetraynoic acid, 3-amino-1-m-(trifluoromethyl)-phenyl-2-pyrazoline (BW 755C), and indomethacin. All drugs inhibited NK lysis at the post-target cell-binding level at concentrations that also suppressed lipoxygenation of arachidonic acid, suggesting that such reactivity may be required for effector cell triggering. NDGA gave a 50% NK cell inhibition in the range of 10-30 microM and also suppressed antibody-dependent and lectin-dependent systems. Further evidence of the involvement of arachidonic acid lipoxygenation was found as NK activity could be reconstituted to NDGA-suppressed effector cells with several metabolites such as LTB4, LTB4 analogues, and hydroxyeicosatetraenoic acids lipoxygenated at C-5, C-12, and C-15. Cyclic nucleotides such as cGMP and cAMP could also reconstitute activity with optimal effects at approximately 10(-8) M. The combined evidence is compatible with a model for triggering lysis in which lipoxygenation products have a second messenger function. Whether arachidonic acid lipoxygenation is necessary for effector cells at all different activation/differentiation stages and whether the lipoxygenation products activate guanylic cyclase, protein kinase C, or some other target molecule remain to be further investigated.     

Limitations of Embolic Protection in Saphenous Vein Graft Intervention: Insights from 202 Consecutive Patients

Between January 2003 and September 2006, a total of 2,541 patients had percutaneous coronary intervention (PCI). Of these, 202 (226 grafts) had at least one saphenous vein graft (SVG) intervention. Adjunctive distal embolic protection (DEP) devices were attempted in 123 SVGs (54.4%). The 30-day major adverse cardiac event (occurrence of death, myocardial infarction, or target vessel revascularization) rate in the overall group was 11.9%. The presence of angiographic thrombus independently predicted DEP use while the presence of in-stent restenosis predicted no DEP use. Although the presence of all angiographic technical feasibility criteria independently predicted DEP use, only 72 (32.4%) and 33 (14.6%) of the SVGs would have been eligible for the occlusive balloon- and filter-based distal embolic criteria, respectively. The most common technical reason for ineligibility was a graft size smaller than 3.0 mm, followed by the lack of a long enough landing zone. In a subset of 21 (9.3%) completely occluded lesions which would have excluded DEP use, angiographic success was 66.7%, and that was predicated on successful debulking with rheolytic thrombectomy in 13 (61.9%) with subsequent DEP in 5 (23.8%). In conclusion, not all grafts can be protected, and even in those that can, such protection may be incomplete. Newer embolic protection devices, such as the Proxis^®, were recently introduced to expand the applicability to a wider population of vein grafts. However, further design improvements such as device miniaturizations applicable to sub-3.0-mm vessels and better particle removing/filtering mechanisms are needed in order to expand the use of embolic protection to reduce the persistently high complication rates associated with this difficult- to-treat subset of patients.     

Transcriptional and post-transcriptional regulation of granulocyte-macrophage colony-stimulating factor production in human growth factor dependent M-07e cells

Summary. Human myeloid leukaemia cell lines have been shown to differentiate into distinct cell lineages in vitro in response to several differentiation-inducing agents. A human eosinophilic leukaemia cell line, EoL-1, has been shown to differentiate into mature eosinophilic granulocytes by treatment with the culture supernatant of a human T-cell line, HIL-3. In this study we have studied whether the EoL-1 cell line has potential to differentiate into cell lineage other than eosinophils. We found that EoL-1 cells cultured in the presence of tumour necrosis factor (TNF)-α (10u/ml) and interferon (IFN)-γ (1000u/ml) for 2–4d differentiated into macrophage-like cells in morphology, and expressed CD14 antigen on their cell surface. It is possible that the small subpopulation of EoL-1 cells which contains non-specific esterase (NSE) activity may be preferentially differentiated by TNF-α and IFN-γ. To clarify this issue, we have cloned the EoL-1 cell line and obtained NSE negative and positive sublines. Both EoL-1 sublines differentiated into monocyte/ macrophage-like cells, because: (a) EoL-1 sublines were induced to express CD14 antigen, and (b) they attached firmly to the plastic wells; (c) after differentiation they became strongly positive for NSE staining, and secreted TNF-α in response to the stimulation with lipopolysaccharide; and (d) they exhibited potent phagocytic activity. Therefore, we found that the EoL-1 cell line has the ability to differentiate not only into mature eosinophilic cells but also into monocyte/macrophage cell lineage, suggesting that EoL-1 cells represent immature cells with ability to differentiate into multiple cell lineages.