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H Enright

Publications and source records attributed to H Enright.

34 records · Page 2Linked to original sources
PubMed1995

Late infections after allogeneic bone marrow transplantations: comparison of incidence in related and unrelated donor transplant recipients.

Infectious complications are a major cause of morbidity and mortality after allogeneic bone marrow transplantation (BMT). We have evaluated the incidence of late infections (beyond day +50) in recipients of related (RD) and unrelated donor (URD) allogeneic BMT, factors associated with increased risks of infection, and the impact of the late infections on survival. Between 1989 and 1991, 249 patients received an RD (n = 151) or URD (n = 98) allogeneic BMT at the University of Minnesota and all late infections were investigated. Three hundred sixty-seven late infectious events developed in 162 patients between 50 days and 2 years after BMT. The incidence of any late infection was greater in URD versus RD recipients (84.7% v 68.2%, respectively; P = .009). In multivariate analysis, advanced graft-versus-host disease (GVHD) was significantly associated with late infections. The effect of GVHD was apparent only in RD recipients (relative risk [RR], 2.29; P = .003), whereas URD recipients, with or without GVHD, had more late infections compared with RD recipients without GVHD. Multivariate analysis showed that late posttransplantation infections were the dominant independent factor associated with increased nonrelapse mortality (RR, 5.5; P = .0001), resulting in improved 3-year survival for RD versus URD recipients (49.9% +/- 8% v 34.4% +/- 10%; P = .004). In this study, we observed that late infections are more frequent in URD recipients, resulting in substantially higher nonrelapse mortality. This prolonged period of increased infectious risk in URD recipients suggests the need for aggressive surveillance and therapy of late infections and perhaps prolonged antibiotic prophylaxis for all URD BMT recipients.

Adolescent↗
PubMed1995

White cell reduction in platelet concentrates and packed red cells by filtration: a multicenter clinical trial. The Trap Study Group.

BACKGROUND: Most previous studies on white cell (WBC) reduction by filtration have been small-scale studies conducted under tightly controlled laboratory conditions. Their results would be the ideal, rather than what might be expected during routine operation. STUDY DESIGN AND METHODS: To obtain information on routine filtration of blood components, data have been collected from a large-scale, ongoing, multicenter clinical trial designed to determine the effectiveness of WBC reduction in or ultraviolet B radiation of platelet concentrates before transfusion in preventing platelet alloimmunization and platelet transfusion refractoriness. The WBC content of blood components both before and after filtration was determined by automated cell counters and a manual propidium iodide-staining method, respectively. Platelet and red cell losses during filtration were measured. RESULTS: The average platelet losses after filtration were 24 +/- 15 percent and 20 +/- 9 percent for apheresis platelets and pooled platelets, respectively. The frequencies at which filtered platelet concentrates contained high levels of residual WBCs (> 5 x 10(6)) were 7 percent and 5 percent for apheresis platelets and pooled platelets, respectively. Further analysis of the platelet filtration data showed that greater numbers of total initial WBCs in the pooled platelets were associated with increased percentages of filtration failure (> 5 x 10(6) residual WBCs). For packed red cells, the average losses during filtration were 23 +/- 4 percent and 15 +/- 3 percent for CPDA-1 units and Adsol units, respectively. The frequencies at which filtered red cells contained > 5 x 10(6) residual WBCs were 2.7 percent for one type of filter and 0.3 percent for another type of filter. CONCLUSION: There were significant losses of platelets during filtration, which could add to the costs of WBC reduction and lead to possible increases in donor exposures. Filtration failures still occurred, despite careful observation of the standard filtration procedures. The number of total WBCs in pooled platelets before filtration has been identified as an important factor in determining the success of WBC reduction.

Blood Platelets↗
PubMed1995

Chronic myelogenous leukemia.

Chronic myelogenous leukemia is a clonal hematopoietic malignancy characterized by a balanced translocation between chromosomes 9 and 22 that results in the generation of an abnormal bcr/abl fusion protein with increased tyrosine kinase activity. This abnormal fusion protein has transforming activity for hematopoietic cells in vitro and causes chronic myelogenous leukemia-like myelopoiesis in mice. Chronic myelogenous leukemia progenitor cells display abnormalities in their interactions with bone marrow stroma, perhaps due to defective adhesion molecule function. Conventional therapies for chronic myelogenous leukemia include hydroxyurea, busulfan, or interferon. Treatment with interferon may prolong overall survival, especially in patients who achieve a cytogenetic response. Related donor marrow transplantation can result in long-term survival in more than 65% of patients treated early in the course of disease. For patients without an available matched sibling donor, unrelated donor marrow transplantation or autologous marrow transplantation are alternative therapeutic options.

Animals↗
PubMed1995

Paraneoplastic autoimmune phenomena in patients with myelodysplastic syndromes: response to immunosuppressive therapy.

We analysed the clinical features, course and response to immunosuppressive therapy in 30 patients with autoimmune disorders associated with myelodysplastic syndromes (MDS). 18 patients with MDS developed acute systemic autoimmune disorders. Common manifestations were skin vasculitis (n = 15) and arthritis (n = 11). Seven patients had an acute clinical syndrome of vasculitic skin rash, fever and arthritis with peripheral oedema in three and pulmonary infiltrates in five of these seven patients. Other acute manifestations included pericarditis, pleural effusions, skin ulceration, seizures, myositis and peripheral neuropathy. Chronic or isolated autoimmune manifestations (n = 11) included glomerulonephritis, polyneuropathy, pyoderma gangrenosum, ulcerative colitis and polyarthritis. Classic connective tissue disorders recognized included relapsing polychondritis, polymyalgia rheumatica, Raynaud's syndrome and Sjögren's syndrome. Autoimmune manifestations responded to immunosuppressive therapy (primarily prednisone) in 26/27 patients treated. Furthermore, cytopenias improved substantially in six patients, including complete normalization of peripheral blood counts in two patients with cytogenetic remission in one. Patients with a haematological response to immunosuppressive therapy had improved survival compared with non-responding patients. The autoimmune syndrome was implicated as a primary cause of death in 8/17 patients who died. Autoimmune manifestations may be more common than previously recognized in patients with MDS. Aggressive therapy with immunosuppressive agents in selected patients often controls autoimmune phenomena associated with MDS and may lead to haematological responses in some patients.

Adolescent↗
PubMed1994

Effect of pyruvate on oxidant injury to isolated and cellular DNA.

Drawing upon the capacity of pyruvate to detoxify H2O2, we demonstrate that pyruvate (i) protects against H2O2-dependent, hydroxyl radical-mediated degradation of isolated DNA; (ii) reduces the amount of 8-hydroxy-2-deoxyguanosine detected following oxidative injury to isolated DNA and (iii) diminishes the amounts of detectable hydroxyl radical generated by a H2O2-dependent system. Compared to mannitol, pyruvate protects weakly against oxidative degradation of DNA induced by a H2O2-independent, hydroxyl radical-generating system. The protective effects of pyruvate against H2O2-instigated DNA damage were also evinced in cells in culture exposed to H2O2. In contrast to its protective effects against H2O2-dependent injury to DNA, pyruvate failed to offer convincing protection to another intracellular, H2O2-vulnerable target, glyceraldehyde-3-phosphate dehydrogenase. The protection conferred by pyruvate to intracellular H2O2-vulnerable targets is thus influenced by the nature of the target exposed to H2O2. Pyruvate was markedly protective in a model of cytotoxicity induced by the concomitant depletion of cellular glutathione and inhibition of catalase activity; pyruvate can thus function as an intracellular antioxidant and in this latter model, no evidence of DNA damage was observed. Pyruvate, in contrast to catalase, is a potent protector against cytotoxicity induced by organic peroxides, a finding that cannot be explained by the scavenging of organic peroxides, differences in glutathione content or attenuation in oxidative injury to DNA. We conclude that while DNA damage is a key pathogenetic event in oxidative stress induced by H2O2, such nuclear changes may not universally subserve a critical role in models of H2O2-dependent cell death. We also conclude that the antioxidant capabilities of pyruvate extend beyond scavenging of H2O2 to include potent protection against cytotoxicity induced by organic peroxides.

Animals↗
PubMed1994

Bone marrow transplantation for chronic myelogenous leukemia: clinical outcomes.

Marrow transplant is potentially curative therapy for CML. Allogeneic sibling-donor marrow transplant may be the therapy of choice for younger patients early in the course of disease. Early transplant is an important influence on disease-free survival and relapse after related-donor transplant therapy, although additional patient characteristics influencing outcome can be identified and may have cumulative adverse effects. The 5-year disease-free survival of patients transplanted within one year of diagnosis and without signs of advanced disease is greater than 65%. Significant problems remain, however, including early mortality (primarily from infection, pneumonia, and pneumonitis) and relapse of CML following transplant, including late relapse occurring more than 5 years posttransplant. For patients without a matched, related donor, unrelated-donor marrow transplant may be a treatment option and can result in successful outcome for patients with CML. Relapse following unrelated-donor marrow transplant is rare. However, the use of an unrelated donor is associated with significant toxicity, including early mortality, engraftment failure, and ongoing morbidity and mortality associated with acute and chronic graft-versus-host disease. For patients who lack an available matched-related or -unrelated donor, autologous marrow transplant has been developed as an alternative approach to therapy. Long-term survival following autologous marrow transplant is possible and may even approach the survival for allogeneic related-donor recipients, although cure of disease is not achieved.

Actuarial Analysis↗
PubMed1994

Internucleosomal cleavage of DNA as the sole criterion for apoptosis may be artifactual.

Apoptosis is a distinct form of cell death characterized by internucleosomal cleavage of DNA, cell membrane blebbing, condensation of nuclear chromatin in the nuclear periphery, and the formation of apoptotic, condensed nuclear bodies. The finding of internucleosomal cleavage of chromatin, perhaps caused by endonuclease activation, has become accepted as a hallmark of this form of cell death. We describe the incidental and artifactual finding of internucleosomal cleavage of chromatin from kidney tissue from normal animals. Nephrectomy was performed in living animals, and renal tissue was digested with proteinase K in 10 mmol/L Tris, 1 mmol/L ethylenediaminetetraacetic acid (EDTA), 10 mmol/L NaCl, and 0.5% sodium dodecyl sulfate. Agarose gel electrophoresis of extracted DNA showed internucleosomal cleavage. Internucleosomal cleavage of DNA was not tissue specific but was evident also in liver DNA from a number of animals. Histologic examination of kidney tissue where DNA exhibited internucleosomal cleavage showed normal morphology, with no evidence of either apoptotic or necrotic cell death. Cleavage was not completely prevented by immediate freezing of kidney tissue in liquid nitrogen before DNA extraction, nor was it prevented by the addition of spermidine, of ethyleneglycol-bis-(beta-aminoethylether)-N,N,N',N'-tetraace tic acid, of phenylmethylsulfonylfluride, or by an increased concentration of NaCl to 100 mmol/L in the digestion buffer. Internucleosomal cleavage of DNA was mostly, although not invariably, inhibited by the use of a digestion buffer containing 10 mmol/L Tris, 25 mmol/L EDTA, and 100 mmol/L NaCl. "Apoptotic" chromatin changes (internucleosomal fragmentation) are not always associated with histologic evidence of apoptosis and may occur artifactually.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Tumor cell heme uptake induces ferritin synthesis resulting in altered oxidant sensitivity: possible role in chemotherapy efficacy.

Neovascularization and hemorrhage are common features of malignant tumors. We wondered whether hemoglobin derived from extravasated RBC deposits heme-derived iron into the tumor, which could modulate the sensitivity of cancer cells to oxidant-mediated injury. A brief exposure (1 h) of 51Cr-radiolabeled breast cancer cells (BT-20) but not colon cancer cells (Caco-2) to hemin (10 microM) or FeSO4 (10 microM) significantly enhances cytotoxicity mediated by 0.5 mM hydrogen peroxide (H2O2). Associated with Caco-2 resistance, these cells were found to be enriched in the endogenous iron chelator, ferritin. If cellular ferritin is even further increased through 1 h incubation (24 h prior to H2O2 exposure) of both cell types with hemin, FeSO4, or exogenous spleen apoferritin itself (24 h), marked resistance to H2O2-mediated cytotoxicity is manifest. Under several conditions, the sensitivity of tumor cells to oxidant-mediated lysis is inversely proportional to their ferritin content. Pretreatment of BT-20 and Caco-2 cells with hemin or FeSO4 rapidly increases H-ferritin mRNA but only slightly increases L-ferritin mRNA; nevertheless, large increases in overall ferritin content of iron-exposed cells result. Data analogous to those with H2O2-mediated cytotoxicity were obtained in studies of bleomycin-engendered DNA strand breakage and cell damage, i.e., brief treatment of BT-20 cells with both hemin or FeSO4 significantly increases their sensitivity to bleomycin (100 micrograms/ml), whereas treatment followed by 24 h incubation with media alone significantly protects against bleomycin toxicity. We speculate that acute exposure of tumors to iron (e.g., derived from heme-proteins in hemorrhagic cancerous lesions) may increase sensitivity of some cancer cells, particularly those relatively low in endogenous ferritin, to oxidant-mediated lysis. In contrast, repeated, more chronic, exposure effector cells or chemotherapeutic agents, an effect derived from their increased synthesis and accumulation of the intracellular iron scavenger, ferritin.

Antineoplastic Agents↗
PubMed1993

Cytomegalovirus pneumonia after bone marrow transplantation. Risk factors and response to therapy.

Cytomegalovirus pneumonia complicated bone marrow transplantation in 75 (63 allogeneic and 12 autologous) of 1136 recipients (Kaplan-Meier incidence 8.8%). CMV pneumonia occurred more frequently in allogeneic (12.4%) than autologous recipients (3.3%). Increased risk for CMV pneumonia was observed in allogeneic recipients who were seropositive (relative risk = 2.9), older age (RR = 1.4 per decade), those conditioned with total-body irradiation (RR = 2.7), who received antithymocyte globulin (RR = 2.9) or T cell-depleted marrow (RR = 2.7) or who had CMV viruria (RR = 4.0) or viremia (RR = 5.9). Autologous recipients were also at increased risk if they were seropositive (RR = 6.1), or developed viruria (RR = 7.0) or viremia (RR = 15.4). Thirteen of 14 untreated patients died without improvement. Prognosis was poor in patients who were ventilator-dependent at initiation of therapy (median survival 17 days), with only 1 long-term survivor. In contrast, patients ventilator-independent at initiation of therapy with ganciclovir and immunoglobulin (n = 22) had a median survival of > 274 days, with 9 long-term survivors. Ganciclovir alone or acyclovir with immunoglobulin in ventilator-independent patients was less effective (median survivals 80 and 10 days, respectively). Overall, 10 of 75 patients were surviving 10-73 months (median 47) from diagnosis; 9 of these were ventilator-independent at initiation of therapy and received ganciclovir with immunoglobulin. CMV pneumonia was less common, but was severe in autologous recipients, with only 2 of 12 surviving. CMV pneumonia remains a prominent cause of death following BMT. Early therapy with ganciclovir and immunoglobulin before respiratory failure supervenes may improve survival.

Acyclovir↗
PubMed1992

Inversion of chromosome 16 and dysplastic eosinophils in accelerated phase of chronic myeloid leukemia.

Abnormalities of chromosome 16, including inv(16)(p13q22), del(16)(q22), and t(16;16)(p13;q22), have been reported almost exclusively in association with acute myelomonocytic leukemia and are characteristically accompanied by abnormal eosinophils with dysplastic granules in the bone marrow. We observed an inv(16)(p13q22) in two patients with typical Philadelphia chromosome positive chronic myeloid leukemia (CML). The appearance of the abnormality of chromosome 16 was associated with acceleration of disease or onset of blast crisis and with the appearance in the bone marrow of abnormal eosinophils. In both cases the marrow karyotypes were 46,XY,t(9;22)(q34;q11)/46,XY,inv(16)(p13q22),t(9;22)(q34;q11). In these two patients the temporal association of the acquisition of the inversion 16 and the appearance of monocytoid cells and dysplastic eosinophils in the bone marrow further supports the relationship of this karyotypic abnormality with leukemic monocytoid and eosinophilic evolution. This secondary cytogenetic change appears to be an infrequent manifestation of specific phenotypic disease progression in CML.

Adult↗
PubMed1990

Avascular necrosis of bone: a common serious complication of allogeneic bone marrow transplantation.

PURPOSE: To describe the incidence, presentation, clinical course, and management of avascular necrosis of bone following bone marrow transplantation, and to identify risk factors related to its development and outcome. PATIENTS AND METHODS: All patients developing avascular necrosis after transplantation between March 1974 and May 1988 were identified by means of the Minnesota Bone Marrow Transplant Database and hospital records and included in analysis. Of 902 consecutive patients undergoing bone marrow transplantation, 28 developed avascular necrosis of bone. RESULTS: Twenty-eight of 642 allogeneic transplant recipients (10.4% by product limit estimate) developed avascular necrosis compared to zero of 260 autologous transplant recipients. Symptoms developed 1 to 62 months (median 12 months) after transplantation. In the 28 patients a total of 91 joints were affected (mean 3.3 per patient, range one to eight joints). The hip joint was most often involved (64% of patients), followed by knee (61%), ankle (29%), shoulder (21%), and elbow (7%). Initial standard radiographs were negative in 13 patients, while in nine patients, technetium-99 scans and/or magnetic resonance imaging demonstrated changes of osteonecrosis before changes on routine radiographs. Almost all patients had received steroid prophylaxis and therapy for graft-versus-host disease (GVHD). We observed a significant correlation between the total cumulative dose of steroids and number of joints involved (p less than 0.01). A multivariate analysis (allogeneic transplant patients only) identified acute or chronic GVHD requiring steroid therapy (p = 0.003), and increasing age (p = 0.002) as significant and independent risk factors. Fourteen patients required surgery, including joint replacement in 11 patients. In six of six patients, hip core decompression failed to halt disease progression, and total hip arthroplasty was subsequently required. CONCLUSION: Avascular necrosis of bone is a frequent late complication of bone marrow transplantation, causing significant morbidity and often requiring surgery; diagnosis using conventional imaging techniques may be difficult and treatment remains inadequate.

Adolescent↗
PubMed1990

C-reactive protein concentrations pre- and post-transfusion.

In a prospective study, serum C-reactive protein (CRP) levels were analysed before and after 18 transfusional episodes, using a fluorescence polarization immunoassay. Only patients with a stable CRP value for two consecutive days before transfusion were assessed. Although small rises in CRP concentrations occurred following 55.6% of transfusions, there was no statistically significant difference between pre- and post-transfusion CRP values, and these increases also failed to reach clinical significance. An increase in CRP post-transfusion of greater than 100 mg/l occurred on only one occasion, and was more likely to be due to underlying infection.

Blood Transfusion↗
PubMed1989

Clot lysis by gastric juice: an in vitro study.

Gastric juice from patients with peptic ulcer disease and from patients with no upper gastrointestinal abnormality was studied in order to assess its effect on a formed fibrin clot. In both groups of patients gastric juice caused a marked increase in fibrinolysis as evidenced by a shortening of the euglobulin clot lysis time. This plasmin mediated fibrinolytic activity was found to be heat labile and only present in an acid environment. Addition of tranexamic acid or sucralfate to gastric juice almost completely reversed this effect, whereas pepstatin was only partially effective. It is probable that acid dependent proteases other than pepsin are responsible for the marked fibrinolysis. The ulcer healing agent sucralfate might be useful in those patients at risk of bleeding or rebleeding from active peptic ulcer disease.

Fibrinolysis↗
PubMedDate not supplied

Autologous stem cell transplantation in myeloma: the St James's Hospital experience, 1997-2003.

BACKGROUND: High-dose treatment with autologous stem cell transplantation (ASCT) has become the standard of care for patients with myeloma below the age of 65 years. AIMS: We report an audit of 60 patients (median age: 52.5 years) who underwent ASCT in the National Bone Marrow Transplant centre in St James's Hospital in Dublin between 1997 and 2003 inclusive. METHODS: Clinical and laboratory data were retrieved from patient medical records and hospital information management systems. RESULTS: Thirty-six patients had IgG, 11 IgA, 1 IgD, 9 light chain and 3 non-secretory MM. Fifty-seven (95%) patients received anthracycline-corticosteroid combination chemotherapy prior to autografting. There was no transplant-related mortality (TRM). Complete (CR) and Partial Responses (PR) were seen in 16 (29.6%) and 29 (53.7%) of those evaluable (n = 54 (90%)). The actuarial Progression-Free (PFS) and Overall Survival (OS) rates at five years are 13% and 55% respectively. CONCLUSION: Centre outcome is comparable to published international series and supports the use of ASCT in the treatment of this malignancy.

Aged↗