Biologic effects of leukocytes present in transfused cellular blood products

A considerable literature has accumulated over the past decade indicating that leukocytes present in allogeneic cellular blood components, intended for transfusion, are associated with adverse effects to the recipient. These include the development of febrile transfusion reactions, graft-versus-host disease, alloimmunization to leukocyte antigens, and the immunomodulatory effects that might influence the prognosis of patients with a malignancy. Moreover, it has become evident that such leukocytes may be the vector of infectious agents such as CMV, HTLV-I/II, and EBV as well as other viruses. An interesting development that has occurred coincidentally in transfusion medicine is that agencies responsible for the provision of blood products are being designated manufacturers of biologicals. The trend among manufacturers of biologicals is to try to produce pure products to provide for the specific therapeutic need of patients. Thus, with the realization that allogeneic leukocytes and their products may have adverse biologic activities, there is increasing pressure from various sources for the reduction of the leukocyte content in allogeneic blood components to minimize the occurrence of their adverse effects. Although the threshold leukocyte number below which these effects might no longer occur is still to be determined, a 2 to 3 log10 leukocyte reduction, provided by the currently available commercial leukocyte filters, has been shown to reduce the frequency of many of such reactions. On the other hand, the immunosuppressive effects produced by the infusion of allogeneic leukocytes might be beneficial for some patients, ie, for the maintenance of kidney allografts, in possibly reducing the relapse rate in patients with inflammatory bowel diseases, and in ameliorating recurrent spontaneous abortion. Moreover, therapeutic granulocyte transfusions may be of benefit in certain well- defined categories of patients infected with bacteria, yeast, and/or fungi. These include neonates with bacterial sepsis associated with bone marrow failure as well as severely neutropenic leukemic patients with an infection unresponsive to appropriate and specific antibiotic therapy. Many of the results obtained with the use of leukocyte depletion filters are tantalizing, but the actual clinical benefit of leukodepletion has not been established in most instances, because much of the available data are retrospective or from uncontrolled clinical trials. Moreover, issues of cost-effectiveness and quality control have not been considered adequately. Properly designed prospective clinical trials are essential to provide data with which to answer such questions and also to help define the optimal conditions required for the preparation of blood components ultimately destined for clinical use. Only with the availability of such data can sound decisions be made about the clinical value of leukodepletion.     

Intermediate lymphocytic lymphoma: immunophenotypic and cytogenetic findings

A detailed immunohistologic and cytogenetic analysis of 12 cases of intermediate lymphocytic lymphoma was performed. The characteristic immunophenotype of intermediate lymphocytic lymphoma was: surface IgM and IgD+, BA1+, B1+, BA2-, B2-, B4+, Leu 14+, Leu 1+, HLA-DR+, and common acute lymphocytic leukemia associated (CALLA) antigen negative. Clonal chromosome abnormalities were identified in ten cases, with structural or numerical abnormalities of chromosomes 11 or 12 in nine cases. Five cases had structural abnormalities involving the long arm of chromosome 11; three of these had translocations with chromosome 14 at band q32. Three cases had trisomy 12, and one case had a translocation involving the long arm of chromosome 12. The tenth case had a translocation involving the long arms of chromosomes 7 and 9. These characteristic immunophenotypic and cytogenetic findings suggest a close lineage relationship between intermediate lymphocytic lymphoma and small lymphocytic (well differentiated) lymphoma/chronic lymphocytic leukemia. Their differing clinical, cytologic, and architectural features suggest, however, that intermediate lymphocytic lymphoma should be considered a separate category of lymphocytic lymphoma in the International Working Formulation.     

Successful Results of a Bipolar Active Fixation Lead for Atrial Application: An Interim Analysis

Adequate atrial lead performance consists of stable sensing and pacing properties. To evaluate whether the CPI 4269 bipolar lead, covered with mannitol (Sweet Tip), in the atrial position encounters these properties, we performed a prospective study of this lead. After complete dissolution of the mannitol helix, mapping of the atrium to obtain the highest electrogram and lowest threshold was followed by screw-in into the endocardium. Intraoperative measurements were performed and long-term follow-up was scheduled every 6 to 12 months to measure threshold and perform an intracardial electro-gram. Between February 1993 and December 1996, a total number of 73 leads in the atrial position in a consecutive series of patients was implanted. Implantation was performed in 28 patients receiving an AAIR and 45 patients a DDDR pacemaker. Reason for pacemaker implantation was a third-degree AV block in 37% of patients, type II second-degree AV block in 25%, sick sinus syndrome in 35%, and drug refractory paroxysmal atrial fibrillation following His-bundle ablation in 3%. The intraoperative bipolar atrial electrogram had a mean voltage of 4.25 ± 2.1 mV. The acute atrial bipolar threshold was 0.63 ± 0.43 V, and current was 1.35 ± 0.81 mA at a 1.0-ms pulse duration. The mean acute resistance of the lead was 572 ± 86 Ohm. After a mean follow-up of 18.3 months, the bipolar intracardial electrogram was 3.37 ± 2.00 mV, the mean atrial threshold measured at the last outpatient clinic visit was 0.99 ± 0.74 V and the mean impedance was 640 ±127 Ohm. A sensing problem due to traction of the atrial lead occurred in only one patient. Acute and late dislodgement did not occur. The CPI 4269 (Sweet Tip) lead is manufactured with a dissolvable capsule covering the helix tip electrode, permitting a safe passage through the venous system. This interim analysis shows that this lead in the atrial position has favorable acute and chronic results.     

Percutaneous angioplasty in clinical management of renovascular hypertension: initial and long-term results

Between January 1980 and July 1983, percutaneous transluminal angioplasty was attempted on 137 stenotic renal arteries in 100 patients. At termination of follow-up studies (3-39 months, mean of 16 months), 70% of those treated for hypertension had benefited from the procedure. Stenosis secondary to fibromuscular dysplasia responded better than stenosis from arteriosclerosis (85% and 65% of the patients, respectively). Benefit was minimal for those with stenosis of the renal artery ostium or renal insufficiency. Determining levels of renal vein renin before angioplasty is helpful in selecting patients; following angioplasty, this has considerable significance in predicting the success of the procedure.     

The Enhancing Effect of Spawning on Elimination of a Persistent Polychlorinated Biphenyl from Female Yellow Perch

The Enhancing Effect of Spawning on Elimination of a PersistentPolychlorinated Biphenyl from Female Yellow Perch. VODICNIK,M. J., AND PETERSON, R. E. (1985). Fundam. Appl. Toxicol. 5,770–776. Distribution and elimination of 2,5,2',5'-tetrachloro[¹⁴C]biphenyl.(4-CB) were studied for 6 months after exposing sexually maturefemale yellow perch to the compound in water and transferringthem to flowing 4-CB-free water. Perch that were exposed inJanuary spawned in May, and the study was terminated in June.During the first 4 months after exposure, the t for whole-bodyelimination was 22 weeks, primarily by elimination of 4-CB fromthe viscera and carcass. During spawning, enhanced elimination(t < 0.7 weeks) was due to the voiding of eggs containing4-CB. After spawning, whole-body elimination returned to a slowerrate (t = 16.3 weeks). Prior to the enhancement in 4-CB eliminationrate during spawning, there was a redistribution of 4-CB residueswithin the body of the perch which was characterized by a transferof 4-CB residues from primarily the carcass and viscera to eggs.Two weeks after exposure, 30% of the initial 4-CB body burdenwas distributed to the eggs, whereas just prior to spawning,about 50% was present in this tissue. These findings demonstratethat egg maturation and spawning result in a significant reductionin the body burden of a persistent polychlorinated biphenylin a lean-fish species.     

Long-Term Follow-Up of Corridor Operation for Lone Atrial Fibrillation:

Late Results of Surgery for AF. Introduction: Currently, surgery- and catheter-mediated ablation is applied when drug refractoriness of atrial fibrillation is evident, although little is known about the long-term incidence of new atrial arrhythmia and the preservation of sinus node function.
Methods and Results: To address this issue, 30 patients with successful corridor surgery for lone paroxysmal atrial fibrillation and normal preoperative sinus node function were followed in a single outpatient department. Five years after surgery, the actuarial proportion of patients with recurrence of atrial fibrillation arising in the corridor was 8%± 5%, with new atrial arrhythmias consisting of atrial flutter and atrial tachycardia in the corridor 27%± 8%, and with incompetent sinus node requiring pacing therapy 13%± 6%. Right atrial transport was preserved in 69% of the patients without recurrence of atrial fibrillation and normal sinus node function. Stroke was documented in two patients.
Conclusions: Corridor surgery for atrial fibrillation is a transient or palliative treatment instead of a definitive therapy for drug refractory atrial fibrillation. This observation strongly affects patient selection for this intervention and constitutes a word of caution for other, non-pharmacologic interventions for drug refractory atrial fibrillation.     

New methodology for evaluating osteoclastic activity induced by orthodontic load

Orthodontic tooth movement (OTM) is a dynamic process of bone modeling involving osteoclast-driven resorption on the compression side. Consequently, to estimate the influence of various situations on tooth movement, experimental studies need to analyze this cell.

Objectives

The aim of this study was to test and validate a new method for evaluating osteoclastic activity stimulated by mechanical loading based on the fractal analysis of the periodontal ligament (PDL)-bone interface.

Material and Methods

The mandibular right first molars of 14 rabbits were tipped mesially by a coil spring exerting a constant force of 85 cN. To evaluate the actual influence of osteoclasts on fractal dimension of bone surface, alendronate (3 mg/Kg) was injected weekly in seven of those rabbits. After 21 days, the animals were killed and their jaws were processed for histological evaluation. Osteoclast counts and fractal analysis (by the box counting method) of the PDL-bone interface were performed in histological sections of the right and left sides of the mandible.

Results

An increase in the number of osteoclasts and in fractal dimension after OTM only happened when alendronate was not administered. Strong correlation was found between the number of osteoclasts and fractal dimension.

Conclusions

Our results suggest that osteoclastic activity leads to an increase in bone surface irregularity, which can be quantified by its fractal dimension. This makes fractal analysis by the box counting method a potential tool for the assessment of osteoclastic activity on bone surfaces in microscopic examination.