Beneficial effect of HLA-A and B matched pretransplant blood transfusions on primary cadaveric kidney graft survival

The effects of HLA-A and B matched pretransplant blood transfusions on the survival of a primary cadaveric kidney graft were studied prospectively in a group of 15 patients who had never received a transfusion and had never been pregnant. Kidney graft survival at one year was 87%, whereas a group of 14 nontransfused patients who underwent transplantation in the same center (before this study was initiated) had a graft survival of only 7%. Twenty-six patients who received a transplant in the same center just before and after each protocol patient served as controls. There were no prior pregnancies in this group; all patients had received blood transfusions from random blood bank donors. Kidney graft survival at one year was 76% for this control group, which is not statistically different from that found for the protocol group. Graft survival for the 13 contralateral kidneys from the protocol group donors was only 50% at one year. These kidneys, however, were transplanted in various other centers. From our study, prolongation of kidney graft survival could be demonstrated for patients receiving pretransplant HLA-A-and-B-matched blood transfusions. Sera screening indicated that lymphocytotoxicity might be reduced by pretransplant HLA-A-and-B-matched blood transfusions. The presence of pretransplant antibodies with specificities for HLA-A and/or B could be significantly correlated with poor graft survival.     

Using quantitative methods to improve the diagnostic workup for abdominal pain in children

Introduction

The differential diagnosis of abdominal pain in children can be challenging. We applied quantitative decision-making methods to this process and sought to determine if their use provided measurable benefit.

Methods

After obtaining institutional review board approval, we recorded key elements of the history, physical examination, laboratory, and imaging evaluations along with the cost and the time spent in the emergency department (ED) for children presenting with abdominal pain. Initially, data were collected (group 1, n = 1366 patients) and then presented to the ED pediatricians. For subsequent patients, ED physicians received a sheet specific to that patient's age and sex reporting the most common diagnoses and the elements of the evaluation that had proven most useful (group 2, n = 624 patients). We compared the difference in length of stay and costs before and after intervention, between study groups, by age groups, and separately by sex using a 2-factor analysis of variance.

Results

The diagnostic workup cost less in boys aged 2 to 12 years after the intervention. In boys and girls older than 12 years, the cost trended lower.

Discussion

This study demonstrates that ED physicians equipped with specific information were able to complete their diagnostic evaluation of children presenting with abdominal pain at a lower cost.     

Differential immunogenicity of HLA mismatches in clinical transplantation

Although HLA matching is beneficial in clinical transplantation, it is not feasible to select a completely HLA matched donor for every potential recipient because of the enormous polymorphism of the HLA system. As a consequence, the majority of the recipients will be transplanted with a mismatched donor organ or hematopoietic stem cell transplant. For this large group of patients it is important to take advantage of the differential immunogenicity of HLA mismatches and to select for them a donor with HLA mismatches of low immunogenicity, the so-called acceptable mismatches. The differential immunogenicity of HLA mismatches can be determined by either retrospective analysis of graft survival data or by in vitro assays measuring T-cell and B-cell alloreactivity. A recently developed computer algorithm (HLAMatchmaker) can be instrumental in selecting donors with HLA mismatches, which do not lead to alloantibody formation. The theoretical background and practical implications of this acceptable mismatch approach are discussed.     

The pharmacokinetics and pharmacodynamics of d- and dl-verapamil in rabbits

The pharmacokinetics and pharmacodynamics of d- and dl-verapamil were studied in conscious rabbits in randomized cross-over fashion. Following a single intravenous dose, there was a biexponential decline in plasma concentration with time. No differences were observed in the pharmacokinetic properties of the compounds. The mean (+/- SD) clearances of d- and dl-verapamil were 0.13 +/- 0.03 and 0.12 +/- 0.05 L/min/kg, respectively. The mean (+/- SD) steady-state volume of distribution was 9.7 +/- 5.2 L/kg for d-verapamil and 8.1 +/- 4.1 L/kg for dl-verapamil. No difference was observed between the compounds in their binding to plasma proteins. The mean (+/- SD) half-life in plasma was 98.7 +/- 63.8 min for d-verapamil and 96.3 +/- 38.0 min for dl-verapamil. In contrast to the lack of stereoselective differences in the pharmacokinetic properties of verapamil, there were marked differences in the pharmacodynamics of d- and dl-verapamil. dl-Verapamil appeared to prolong the PR interval to a greater degree than did d-verapamil, consistent with the more potent calcium channel effects of the l-enantiomer. Similarly, dl-verapamil had more potent hypotensive effects compared with the d-enantiomer, which produced no effects on systemic arterial pressure. Chronotropic effects, judged to be caused by autonomic reflexes in response to the hypotensive effects of the compound, were also statistically greater for dl-verapamil than for d-verapamil. These results demonstrate stereo-selective pharmacodynamic effects in vivo of verapamil.     

Evaluation of the Polytetrafluoroethylene-Membrane Ventilation Tube

In an effort to evaluate the safety and efficacy of the currently available polytetrafluoroethylene (PTFE)-membrane ventilation tube, in a group of 41 children, the experimental tube was inserted into one ear and a conventional tympanostomy tube was placed in the other ear. The membrane tubes, except in a few instances, were inserted into ears without effusion. After the procedure the children were forbidden to swim and their ears were protected during bathing. In addition to pneumatic otoscopy, a specially designed tympanometric test—which determined if the membrane tube was functioning—was used to assess the operation of the new device postoperatively. In many of the children, Eustachian tube function studies were also performed on the ears with the conventional tympanostomy tubes. The study was aborted early in the clinical trial period due to the early findings: only 10 of 41 (24%) of the membrane tubes continued to function, the remainder having become occluded; whereas 35 of 41 (85%) of the conventional tympanostomy tubes were found to be still functioning during the same period of observation. Twelve of the 41 membrane tubes had to be removed prematurely and replaced with conventional tympanostomy tubes due to recurrence of middle ear effusion. Scanning electron microscopic studies of the removed tubes revealed blockage of the membrane pores. From the extraordinarily high failure rate of the PTFE-membrane ventilation tube in this study, it is evident that the experimental tube should not replace the conventional tympanostomy tube at this time. The selection of the PTFE covering-membrane on this tube was ill advised, but the rationale of a semipermeable-membrane ventilation tube has merit. However, should another membrane ventilation tube be designed, its routine use must await controlled clinical trials to determine safety and efficacy in humans.