Outcomes of endoscopically harvested saphenous vein for lower extremity bypass.

OJECTIVES: The purpose of this study was to evaluate the outcomes of endoscopically harvested saphenous vein (EHSV) for lower extremity bypass (LEB) surgery. METHODS: Data from 91 consecutive patients who underwent LEB using EHSV between February 2003 and November 2012 were analyzed. Outcomes of interest were wound infection, patency, re-intervention and limb loss. RESULTS: Fifty-eight (64%) and 33 (36%) patients underwent femoropopliteal (FP) and femorotibial (FT) bypass using EHSV. Three (3%) patients had superficial and 1 (1%) deep wound infection. Primary and primary assisted patency at 5 years was 68% and 71% in the FP group and 56% and 65% in the FT group. Six (6%) patients underwent major amputation. No predicting factors for wound infection or graft patency were found. CONCLUSIONS: EHSV carries a low incidence of perioperative wound complication and has a reasonable mid-to-long-term patency regardless of the length of vein harvested.

Dermacentor andersoni transmission of Francisella tularensis subsp. novicida reflects bacterial colonization, dissemination, and replication coordinated with tick feeding.

Ticks serve as biological vectors for a wide variety of bacterial pathogens which must be able to efficiently colonize specific tick tissues prior to transmission. The bacterial determinants of tick colonization are largely unknown, a knowledge gap attributed in large part to the paucity of tools to genetically manipulate these pathogens. In this study, we demonstrated that Francisella tularensis subsp. novicida, for which a complete two-allele transposon mutant library has been constructed, initially infects the midguts of 100% of acquisition-fed Dermacentor andersoni nymphs, with stable colonization and replication during a subsequent molt. Increased dissemination to and marked replication within the salivary gland was closely linked to a second (transmission) feed and culminated in secretion of bacteria into the saliva and successful transmission. Simultaneous testing of multiple mutants resulted in total bacterial levels similar to those observed for single mutants. However, there was evidence of a bottleneck during colonization, resulting in a founder effect in which the most successful mutant varied when comparing individual ticks. Thus, it is essential to assess mutant success at the level of the tick population rather than in individual ticks. The ability of F. tularensis subsp. novicida to recapitulate the key physiological events by which bacteria colonize and are transmitted by ixodid ticks provides a new genome-wide approach to identify the required pathogen molecules and pathways. The identification of specific genes and, more importantly, conserved pathways that function at the tick-pathogen interface will accelerate the development of new methods to block transmission.

Human leukocyte antigen class-I variation is associated with atopic dermatitis: A case-control study.

Atopic dermatitis (AD) is a common immune-medicated skin disease. Previous studies have explored the relationship between Human Leukocyte Antigen (HLA) allelic variation and AD with conflicting results. The aim was to examine HLA Class I genetic variation, specifically peptide binding groove variation, and associations with AD. A case-control study was designed to evaluate HLA class I allelic variation and binding pocket polymorphisms, using next generation sequencing on 464 subjects with AD and 388 without AD. Logistic regression was used to evaluate associations with AD by estimating odds ratios (95% confidence intervals). Significant associations were noted with susceptibility to AD (B*53:01) and protection from AD (A*01:01, A*02:01, B*07:02 and C*07:02). Evaluation of polymorphic residues in Class I binding pockets revealed six amino acid residues conferring protection against AD: A9F (HLA-A, position 9, phenylalanine) [pocket B/C], A97I [pocket C/E], A152V [pocket E], A156R [pocket D/E], B163E [pocket A] and C116S [pocket F]. These findings demonstrate that specific HLA class I components are associated with susceptibility or protection from AD. Individual amino acid residues are relevant to protection from AD and set the foundation for evaluating potential HLA Class I molecules in complex with peptides/antigens that may initiate or interfere with T-cell responses.

Citation indexing and evaluation of scientific papers.

Evaluation by means of citation patterns can be successful only insofar as published papers and their bibliographies reflect scientific activity and nothing else. Such an innocent descrip tion is becoming less and less tenable. The present scientific explosion gave rise to more than a proportional pub lication explosion, which not only re flects the scientific explosion but has its own dynamics and vicious circles. Publication of results is probably the main means of accomplishing the al most impossible task of accounting for time and money spent on research. Inevitably, this puts a premium on quantity at the expense of quality, and, as with any other type of inflation, the problem worsens: the more papers are written, the less they count for and the greater is the pressure to publish more. What makes matters worse is the fact that the sheer volume of the"litera ture" makes it increasingly difficult to separate what is worthwhile from the rest. Critical reviews have become somewhat of a rarity, and editorial judgment is usually relegated to ref erees, who are contemporaries and, per haps, competitors of the authors-a situation which has its own undesirable implications (11, 18). It requires little imagination to discover other vicious circles, all arising from distortion of the primary reasons for publishing the results of scientific inquiry. There are, it is true, signs of ad justment to this crisis, partly due to some easing of the pressure to pub lish at all costs, and partly due to the readers' changing attitudes toward the flood of publications. An increasing amount of research is now being car ried out in the form of collective proj ects in large institutions where publica tion is no longer the standard method of accounting for individual work. At the same time there is apparent an in creasing tendency for scientific journals to polarize into the relatively few leading ones which carry important informa tion and the many subsidiary journals which serve as vehicles for interim lo cal accounting and, in a way, sub stitute for detailed intradepartmental re ports. This division is a result not of some arbitrary decree but of normal competition between journals, as a re sult of which, however, the strong usual ly get stronger and the weak get weaker. Were it not for these changes and also for a striking improvement in abstracting, indexing, and alerting serv ices, most research workers would have found long ago that, even in their own specialized fields, new information is accumulating faster than it can be sorted out. These developments can pro vide only a temporary reprieve, so long as there remains a strong incentive to publish the greatest possible number of papers. A new scale of values based on citations is by no means infallible or, in many cases, even fair, but at least it provides an alternative to the existing one, which is at the root of the crisis. It might, of course, be asked whether wide acceptance of such new stand ards would not lead to deliberate abuses. A little reflection shows that the system is less open to manipula tion than might appear. First, the ref erees are expected to see to it that the submitted papers cite work which is pertinent to the subject. An increased awareness of the usefulness of citation indexing as a tool for retrieval and evaluation will make this aspect of refereeing more important, and what now passes for minor carelessness or discourtesy could easily come to be regarded as serious malpractice. Sec ond, as noted above, careful selection of references is in the author's own interest, because it helps him to reach his readers. There is, therefore, some room for hope that healthy feedback in the system will tend to keep it viable. At the basis of this hope lies the supposition that, in the long run, only good work can ensure recognition. As Martyn (2) has pointed out, as an information-retrieval method, cita tion indexing is rather "noisy." The word noisy may apply even more to the problem of evaluation. Whereas in information retrieval much of the unwanted information can be filtered out by suitable search strategy (2, 6), this is not so easy to do for the pur pose of evaluation, because a simple descendence relationship between papers is still an ideal far removed from actuality (7). The situation would be much better if we could at will exclude all citations which do not indi cate real indebtedness. A scheme of citation relationship indicators, first men tioned by Garfield (12) and elaborated by Lipetz (17), would be a help, but, even if it were technically feasible, to provide such indicators would greatly add to the production costs of the Index. Another possible way to minimize the effects of "noise" is to increase the size of the samples on which the reckon ing is based. Now that research has be come a rather popular occupation, it seems that a kind of public vote may have to be accepted as a factor in evaluation. Since this is the case, there is something to be said for extending the "franchise" to minimize acciden tal effects. An index which attempted to process all scientific publications would be several times the size of the present Index, and, what is more, it would not necessarily be an improve ment as a tool for information retrieval because most of the significant work is already concentrated in the present Index. Whether this attempt will ever be considered worthwhile remains pri marily a matter of policy and eco nomics. In the meantime there is an urgent need for more experience with the existing services. It is not the purpose of this article to advocate evaluation of scientific work by some kind of public opinion poll; its purpose is to recognize a pos sible trend in this direction. Any judg ment by public acclaim is subject to obvious fallacies, but we must not be carried away by the analogy to the Stock Exchange or to electoral prac tices. The fact that, in this case, the "public" consists of authors whose con tributions are generally linked creates quite a new pattern of organization. In this discussion some of the aspects of this pattern have been explored through analogy to idealized genetic or mechani cal network models, but the very uniqueness of the system, with its many self-organizing ramifications, makes it a new field which deserves close study, since these developments may have pro found effects on the future of scientific communication.

Adenoviral vector-mediated rescue of the OMP-null phenotype in vivo.

The use of gene deletion by homologous recombination to determine gene or protein function has wide application in vertebrate neurobiology. An ideal complement to gene deletion would be subsequent gene replacement to demonstrate re-acquisition of function. Here we used an adenoviral vector to replace the olfactory marker protein (OMP) gene in olfactory receptor neurons of adult OMP-null mice and demonstrated the subsequent re-acquisition of function. Our results show that short-term expression of OMP restores the kinetics of electrophysiological responses of OMP-null mice to those of the control phenotype. This adenoviral-mediated rescue of the OMP-null phenotype is consistent with involvement of OMP in olfactory transduction.

Targeted deletion of a cyclic nucleotide-gated channel subunit (OCNC1): biochemical and morphological consequences in adult mice.

The olfactory cyclic nucleotide-gated channel subunit 1 (OCNC1) is required for signal transduction in olfactory receptor cells. To further investigate the role of this channel in the olfactory system, the biochemical and morphological consequences of targeted disruption of OCNC1 were investigated in adult mice. Null as compared to wild-type mice had smaller olfactory bulbs, suggesting compromised development of the central target of the receptor cells. Ectopic olfactory marker protein (OMP)-stained fibers localized to the external plexiform layer reflected the relative immaturity of the olfactory bulb in the null mice. The olfactory epithelium of the knock-out mouse was thinner and showed lower expression of olfactory marker protein and growth-associated protein 43, indicating decreases in both generation and maturation of receptor cells. Tyrosine hydroxylase (TH) expression in the olfactory bulb, examined as a reflection of afferent activity, was reduced in the majority of periglomerular neurons but retained in atypical or "necklace" glomeruli localized to posterior aspects of the olfactory bulb. Double label studies demonstrated that the remaining TH-immunostained neurons received their innervation from a subset of receptor cells previously shown to express a phosphodiesterase that differs from that found in most receptor cells. These data indicate that expression of OCNC1 is required for normal development of the olfactory epithelium and olfactory bulb. The robust expression of TH in some periglomerular cells in the OCNC1-null mice suggests that receptor cells innervating these glomeruli may use an alternate signal transduction pathway.

omega-Oxidation of fatty acids and the acetylation p-aminobenzoic acid.

p-Aminobenzoic acid was fed to normal and alloxan-induced diabetic rats injected with [omega-14C]labeled and [2-14C]labeled fatty acids. The p-acetamidobenzoic acid that was excreted was hydrolyzed to yield acetate which was degraded. The distribution of 14C in the acetates formed when an [omega-14C]labeled fatty acid was injected was similar to that when a [2-14C]labeled fatty acid was injected. This contrasts with the finding that in acetates from 2-acetamido-4-phenylbutyric acid excreted when 2-amino-4-phenylbutyric acid was fed, there was a difference in the distributions of 14C, a difference attributable to omega-oxidation of the fatty acid. Acetylation of p-aminobenzoic acid is then concluded to occur in a different cellular environment than that of 2-amino-4-phenylbutyric acid, one in which omega-oxidation is not functional. When 2-amino-4-phenylbutyric acid was fed and [6-14C]palmitic acid injected, rather than [16-14C]palmitic acid, the distribution of 14C in acetate was the same as when [2-14C]palmitic acid was injected. This indicates that the dicarboxylic acid formed on omega-oxidation of palmitic acid does not undergo beta-oxidation to form succinyl-CoA. Thus, glucose is not formed via omega-oxidation of long-chain fatty acid.

The M-Heart percutaneous balloon mitral Valvuloplasty Registry: initial results and early follow-up. The M-Heart Group.

The initial results, complications and early follow-up of 74 patients undergoing percutaneous balloon mitral valvuloplasty in seven hospitals participating in a multicenter registry are reported. Seventy-four patients with a mean age of 53 years had 75 valvuloplasty procedures performed over a 2.5 year period. Eighty-nine percent of the attempted procedures were completed and resulted in an increase in mean mitral valve area from 1.0 +/- 0.04 to 2.0 +/- 0.1 cm2 (p less than 0.0001); the valve area increased greater than or equal to 50% of the baseline valve area in 73% of the patients. Major complications included procedure-related death (2.7%), cardiac tamponade (6.7%), systemic embolism (2.7%) and emergency surgery (6.7%). At a mean follow-up period of 14.6 months, the condition of the majority of patients had improved, and 89% of 55 patients treated only with valvuloplasty were in New York Heart Association functional class I or II. Thus, hemodynamic and clinical improvement can be obtained in the majority of patients with mitral stenosis treated with balloon valvuloplasty in multiple centers. However, suboptimal results and major complications occurred in a significant number of patients and may limit this procedure to use by experienced operators in hospitals with facilities for cardiac surgery.

Clinical and angiographic determinants of primary coronary angioplasty success. M-HEART Investigators.

Clinical and anatomic determinants of the initial success of percutaneous transluminal coronary angioplasty were prospectively evaluated in 826 patients enrolled in the Multi-Hospital Eastern Atlantic Restenosis Trial (M-HEART). The 639 men and 187 women ranged in age from 31 to 85 years. Successful angioplasty (residual stenosis less than 50% and no major complications) was achieved in 886 (88.6%) of 1,000 lesions. Success rates were uniform among the eight individual centers. Outcome was not influenced by gender, age or other clinical features, including severity and duration of angina, prior myocardial infarction, rest pain, transient ST segment elevation, history of smoking or diabetes. In contrast, procedural outcome was significantly associated with lesion-specific angiographic factors. Stenoses 60% to 74%, 75% to 89%, 90% to 99% and 100% were associated with success rates of 96%, 90%, 84% and 69%, respectively (p less than 0.001). Angioplasty was less successful in calcified than in noncalcified lesions (82% versus 90%, p less than 0.01), in thrombotic than in nonthrombotic lesions (82% versus 90%, p less than 0.05) and in lesions in the right coronary artery than in other vessels (84% versus 90%, p less than 0.01). Outcome was not related to other anatomic variables, including lesion location (proximal versus distal), vessel size, eccentricity, stenosis length or translesional gradient. By multivariate logistic regression, preangioplasty percent stenosis, right coronary artery location and lesion calcification were demonstrated to be significant independent predictors of angioplasty success. Alternative clinical and angiographic variables did not contribute to this regression model.(ABSTRACT TRUNCATED AT 250 WORDS)

Percutaneous excimer laser coronary angioplasty: results in the first consecutive 3,000 patients. The ELCA Investigators.

OBJECTIVES: We report the comprehensive results of the first consecutive 3,000 patients treated in an excimer laser coronary angioplasty registry. BACKGROUND: Excimer laser coronary angioplasty involves the use of a pulsed, 308-nm ultraviolet laser transmitted by optical fibers to reduce coronary stenoses. Preliminary reports have described safety and efficacy profiles in small numbers of patients. METHODS: Patients were enrolled in a prospective, nonrandomized manner. The catheters used were 1.3, 1.6, 2.0, 2.2 and 2.4 mm in diameter, at energy densities up to 70 mJ/mm2. Procedures were performed by standard angioplasty technique with conventional guide catheters. RESULTS: Seventy-five percent of patients were male, 68% were in Canadian Cardiovascular Society functional class III or IV and the cohort included 3,592 lesions. Procedural success (final stenosis < or = 50% without in-hospital Q wave myocardial infarction, coronary artery bypass surgery or death) was 90% and did not differ between the first 2,000 and the last 1,000 patients treated. There was no significant difference in success or complication rates with respect to lesion length, nor were there differences between selected complex and simple lesions. Complications included in-hospital bypass surgery (3.8%), Q wave myocardial infarction (2.1%) and death (0.5%). Coronary artery perforation occurred in 1.2% of patients (1% of lesions) but significantly decreased to 0.4% in the last 1,000 patients (0.3% of lesions). Angiographic dissection occurred in 13% of lesions, transient occlusion in 3.4% and sustained occlusion in 3.1%. Comprehensive lesion morphologic data collected in the latter portion of the study showed the procedure predominantly limited to American College of Cardiology-American Heart Association type B2 and C lesions, with no significant difference in short-term outcome between groups. CONCLUSIONS: Excimer laser angioplasty can be safely and effectively applied, even in a variety of complex lesions not well suited for percutaneous transluminal coronary angioplasty. These types may include aorto-ostial, long lesions, total occlusions crossable with a wire, diffuse disease and vein grafts. Most recent data show a trend for the selection of predominantly complex lesions and a reduction in the incidence of perforation. This procedure may broaden the therapeutic window for the interventional treatment of selected complex coronary artery disease.

Balloon angioplasty versus new device intervention: clinical outcomes. A comparison of the NHLBI PTCA and NACI registries.

OBJECTIVES: We sought to compare outcomes of patients treated in the National Heart, Lung, and Blood Institute (NHLBI) Percutaneous Transluminal Coronary Angioplasty (PTCA) and New Approaches to Coronary Intervention (NACI) registries. BACKGROUND: Coronary angioplasty has numerous shortcomings. New devices for performing coronary interventions have been introduced in an effort to improve clinical outcomes. METHODS: Under the sponsorship of the NHLBI, a registry of consecutive patients treated with PTCA during 1985 to 1986 was established. In 1990, the NHLBI funded a second registry, the NACI. The two registries used the same data coordinating center to collect detailed baseline and follow-up information. RESULTS: Patients enrolled in the NACI registry were older, had undergone more previous bypass surgery procedures and had more stenoses located in bypass grafts than patients in the NHLBI PTCA registry. Procedural success was achieved in 72.1% and 82.6% of patients in the PTCA and NACI registries, respectively; however, in-hospital and 1-year mortality rates were 1.0% versus 1.8% and 3.1% versus 5.9% for the PTCA versus NACI registries, respectively. After risk adjustment, there was no difference in 1-year mortality. Rates of target lesion revascularization (TLR) were 21.5% for the PTCA registry and 24.2% for the NACI registry. NACI registry patients had a higher risk for TLR and the composite end point of death, myocardial infarction or revascularization (relative risk 1.28 and 1.23, respectively). However, the NACI registry patients who received stents tended to have a lower adjusted TLR rate. CONCLUSIONS: This comparative study found no overall superiority of these newer devices in terms of patient survival or freedom from TLR after adjustment for baseline risk profiles. Although technologic improvements (especially improved stenting) continue, these observations highlight the importance of careful assessment of clinical results in the broad population of patients in whom interventions are used.

Bailout and corrective use of Gianturco-Roubin flex stents after percutaneous transluminal coronary angioplasty: operator reports and angiographic core laboratory verification from the National Heart, Lung, and Blood Institute/New Approaches to Coronary Intervention Registry.

OBJECTIVES: We sought to determine the in-hospital clinical outcome and angiographic results of patients prospectively entered into the National Heart, Lung, and Blood Institute/New Approaches to Coronary Intervention (NHLBI/NACI) Registry who received Gianturco-Roubin stents as an unplanned new device. BACKGROUND: Between August 1990 and March 1994, nine centers implanted Gianturco-Roubin flex stents as an unplanned new device in the initial treatment of 350 patients (389 lesions) who were prospectively enrolled in the NHLBI/NACI Registry. METHODS: Patients undergoing implantation of the Gianturco-Roubin flex stent were prospectively entered into the Gianturco-Roubin stent portion of the NHLBI/NACI Registry. Only subjects receiving the Gianturco-Roubin stent as a new device in an unplanned fashion are included. RESULTS: The mean age of the patient group was 61.8 years, and the majority of the patients were men. A history of percutaneous transluminal coronary angioplasty (PTCA) was present in 35.4% of the group, and 16.9% had previous coronary artery bypass graft surgery. Unstable angina was present in 67.7%. Double- or triple-vessel coronary artery disease was present in 55.4%, and the average ejection fraction was 58%. The presence of thrombus was noted in 7.3%, and 7.2% had moderate to severe tortuosity of the lesion. The angiographic success rate was 92%. Individual clinical sites reported that 66.3% of the stents were placed after suboptimal PTCA, 20.3% for abrupt closure and 13.4% for some other technical PTCA failure. Major in-hospital events occurred in 9.7% of patients, including death in 1.7%, Q wave myocardial infarction in 3.1% and emergency bypass surgery in 6%. Abrupt closure of a stented segment occurred in 3.1% of patients at a mean of 3.9 days. Cerebrovascular accident occurred in 0.3%, and transfusion was required in 10.6%. Vascular events with surgical repair occurred in 8.6% of patients. CONCLUSIONS: Despite these complications, the use of this device for the treatment of a failed or suboptimal PTCA result remains promising given the adverse outcome of abrupt closure with conventional (nonstent) treatment.

Dpbx, a new homeobox gene closely related to the human proto-oncogene pbx1 molecular structure and developmental expression.

Recently, a new class of homeodomain containing proteins, pbx1, pbx2, and pbx3 has been described. pbx proteins are most closely related to two yeast regulatory proteins, a1 and alpha 2. Here, we identify and characterize the pbx homolog in Drosophila, designated Dpbx. Dpbx is 95% identical to the pbx proteins within the homeodomain and, more remarkably, is 85% to 88% identical within a 201 amino acid region adjacent to the homeodomain. Cytologically, the Dpbx gene is located on the X chromosome at 14A. mRNA expression is both maternal and zygotic and occurs throughout the life cycle. Prior to full germband retraction, Dpbx is rather ubiquitously present and variations are minor. The most notable feature of Dpbx expression is that after germband retraction, high levels of Dpbx are observed in the anterior portion of the ventral nerve cord.

Hypothermia, a grave prognostic sign in hepatic coma.

Hypothermia is a grave prognostic finding in hepatic coma. Occasionally, it is found in patients whose conditions are stabilized clinically or are improving. When hypothermia occurs, the patients usually die within 24 to 48 hours. All of the patients described herein who eventually improved sufficiently to be discharged from the hospital achieved normal temperatures.

Delay in the prehospital phase of acute myocardial infarction. Lack of influence on incidence of sudden death.

Prehospital delay is considered to be an important cause of out-of-hospital coronary mortality. Behavior of patients and physicians in response to the symptoms of myocardial infarction (MI) or impending out-of-hospital death (OHD) was studied for 107 consecutive acute coronary events in Framingham, Mass. Delay due to inappropriate patient behavior was the most important component of total delay. Delay related to patient-physician contact occurred in two thirds of MI cases and was more than 30 minutes in half of these. Office visits and inappropriate triage by nurses and receptionists were important factors in physician delay. However, 60% to 75% of OHDs occur so rapidly that their prevention by reduction of prehospital delay seems impossible. A strategy for reduction of delay that might be of benefit in preventing some of the remaining OHDs is described.

Age changes in bovine lens endopeptidase activity.

Lens endopeptidase activity and thermal stability have been determined as a function of cell development, cell age, and animal age. Lenses from animals aged 3 months to 15 years (lens weights 1.15-2.80 g) were divided into epithelial (outermost), cortical (peripheral), and nuclear (central) regions. Changes accompanying cell development were determined by measuring specific activity in epithelial (undifferentiated), outer cortical (differentiating), inner cortical (mature) and nuclear (aged) regions of individual lenses. Thermal stability of the enzyme activity obtained from the outer cortical and nuclear regions of the same lenses was also determined. Specific activity and thermal stability were found to decrease as a function of lens cell development. Changes with cell development represent the effects of both differentiation and increasing cell age. To determine the effects of cell age alone, activity was determined in the same population of aged, fully differentiated cells in lenses of different ages. Specific activity decreased as a function of cell age alone. Changes with animal age were determined by comparing cells of the same developmental stage from animals of different ages (e.g., differentiating cells of the cortex in animals 3 months to 15 years old). Specific activity for the cortical region increased with animal age while specific activity in the nuclear region appeared to remain constant or decrease slightly with increasing animal age. Thermal stability of the enzyme activity from the cortex was different in young and adult lenses. The change in stability occurred early in the lifespan and was therefore more closely related to animal development than to aging.

An old drug for a new disease: pentostatin (Nipent) in acute graft-versus-host disease.

Bone marrow transplantation has become the modality of choice for a number of malignant conditions. One of the primary causes of morbidity and mortality following bone marrow transplantation is graft-versus-host disease (GVHD). Moderate to severe acute GVHD affects 9% to 35% of patients undergoing standard allogeneic bone marrow transplantation. The incidence of chronic GVHD is approximately 40% to 50%. In our experience at Johns Hopkins Oncology Center, patients with stages 2, 3, and 4 acute GVHD had median survivals of only 5.4, 3.6, and 2.5 months, respectively, despite treatment. Patients with chronic GVHD do not fare much better. Their overall 10-year mortality rate remains high at 42%. Significant failure rates and toxicities have been associated with all available therapeutic options for GVHD. Pentostatin (Nipent; SuperGen, San Ramon, CA) is currently used to treat a variety of hematologic malignancies. In addition to its antineoplastic effects, considerable immunosuppressive properties have been reported. Pentostatin affects the immune system by decreasing lymphocyte number and function. Its immunosuppressive effect has promise for the treatment of GVHD and warrants further study.

Pentostatin (Nipent): a review of potential toxicity and its management.

Pentostatin (Nipent; SuperGen, San Ramon, CA) is a safe and well-tolerated medication but, like all chemotherapeutic agents, it may be associated with some toxicity. The toxicity seen with pentostatin is dose and schedule dependent and can be minimized by appropriate dosing. The dose of pentostatin should never exceed 4 mg/m2. A dose reduction is required for patients with renal insufficiency. Renal and neurological toxicities may occur, yet are uncommon with appropriate dosing. Nausea and vomiting also occur; however, they are usually controlled with antiemetic therapy. Like the other purine nucleoside analogs, pentostatin is an immunosuppressive drug that may increase the risk of infection, especially with opportunistic organisms. Prophylactic antibiotics should be considered when treating patients with pentostatin.

New approaches to treating malignances with stem cell transplantation.

Stem cell transplantation has been successfully used to treat a wide variety of hematologic malignancies. New and exciting strategies being developed for use in conjunction with transplant will be useful in overcoming tumor resistance. It is now clear that a significant part of the antitumor effect of allogeneic stem cell transplantation is derived from the graft itself and is independent of the preparative regimen. Immune therapy derived from the donor's graft is uniquely suited for killing chemoresistant tumor cells and may prove to be an invaluable tool for decreasing the risk of relapse in patients with advanced disease. Among patients who have relapsed after allogeneic bone marrow transplantation (BMT), an immunologically based antitumor effect may be obtained simply by transfusing T cells obtained by leukopheresis of the original bone marrow donor. Referred to as donor leukocyte infusion (DLI), this technique has been used to obtain complete remissions in relapsed acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), multiple myeloma, non-Hodgkin's lymphoma, myelodysplastic syndrome (MDS), and chronic myeloid leukemia (CML). Another approach that uses the donor's graft to obtain a potent antitumor effect is the combination of nonmyeloablative BMT followed by immunotherapy with DLI. Numerous investigators are exploring ways of combining autologous BMT with immune therapy. Animal studies using tumor vaccines in conjunction with autologous transplantation offer a promising method for eliminating tumor. Patients undergoing autologous transplantation may have marrow that has been contaminated with tumor, which places them at a higher risk of relapse. Attempts have been made to eliminate contaminating tumor from the marrow by purging.