-
[show abstract]
[hide abstract]
ABSTRACT: Bleomycin (Bleo)-induced lung injury in mice serves as an animal model of pulmonary fibrosis. The pathogenesis of pulmonary fibrosis remains unclear, but it comprises both inflammatory and fibrotic components. The cytokine interferon (IFN)-alpha is produced by macrophages and may modulate both fibrogenesis and the determination of T lymphocyte phenotype in pulmonary fibrosis.
To investigate the effect of two preparations of recombinant IFN-alpha (IFN-alphaA/D and IFN-alpha2a) on Bleo-induced lung injury in C57BL/6 mice.
Mice were treated by a single intratracheal (IT) instillation of 0.06 mg of Bleo in 0.1 ml of saline or saline alone. One of two different IFN-alpha preparations, IFN-alphaA/D or IFN-alpha2a in saline, or saline alone were administered by daily intraperitoneal injections starting 1 day prior to IT instillation. The treatment groups were as follows: IT Bleo and intraperitoneal saline; IT Bleo and intraperitoneal IFN-alpha2a; IT Bleo and intraperitoneal IFN-alphaA/D; IT saline and intraperitoneal IFN-alphaA/D or IFN-alpha2a; IT saline and intraperitoneal saline. The animals were sacrificed 14 days after IT instillation. Lung injury was evaluated by total and differential cell count in bronchoalveolar lavage (BAL) fluid, by a semiquantitative morphological index of lung injury and a quantitative image analysis of cellularity and fibrosis fraction and by biochemical analysis of lung hydroxyproline content.
In Bleo-treated mice, IFN-alpha2a treatment caused a significant rise in BAL lymphocytes and in cellularity and fibrosis fractions in lung tissue. In contrast, IFN-alphaA/D treatment had no effect on Bleo-induced lung injury.
IFN-alpha may enhance Bleo-induced lung injury but this effect varies with different IFN preparations.
Respiration 02/2001; 68(2):169-77. · 2.26 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Reliable long-term vascular access is essential for the treatment of patients with acute myeloid leukemia (AML). Although peripherally inserted central catheters (PICCs) have been in use for many years, little data exist on their use in patients receiving intensive chemotherapy. We retrospectively reviewed all AML patients who had a PICC inserted between July 95 and May 98. Fifty two PICCs were inserted in 40 patients with AML. Thirty three PICCs were inserted during severe thrombocytopenia (platelets < 50 x 10(9)/L), and 31 during severe neutropenia (neutrophils < 0.5 x 10(9)/L). Mean catheter duration was 82 (median 63, range 3-441) days for a total of 4274 catheter days. A mean of 1.8 chemotherapy courses were administered via each PICC. There were 5 early complications of PICC placement. Other mechanical complications occurred in 14 catheters and phlebitis in 12. Twenty blood stream infections (BSI) occurred in 17 patients. All BSIs occurred during neutropenia. Seventeen PICCs were removed due to the following complications - phlebitis (11), possible catheter related BSI (4), mechanical reasons in 3 (2 with concomitant phlebitis) and persistent fever (1). PICC duration was significantly shorter in these 17 catheters (52.9 v 96.4 days in the other 35, p=0.0289). We conclude that PICCs provide long-term vascular access with an acceptable complication rate in patients with AML. However, a randomised trial is required before PICCs can be considered an alternative to tunneled central venous catheters in these patients.
Leukemia and Lymphoma 01/2001; 40(3-4):365-71. · 2.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Since transforming growth factor beta (TGF-beta) is presumed to play a role in lung fibrosis, we evaluated the effect of suramin (Sur), a substance with an anti-TGF-beta effect, in vivo on bleomycin (Bleo)-induced pulmonary injury in mice and in vitro on human lung fibroblasts. Four groups of C57BL/6 mice each received one of four treatments: (1) intratracheal (i.t.) instillation of Bleo and intraperitoneal (i.p.) injections of Sur, every other day, starting one day before i.t. instillation of Bleo (Bleo-Sur); (2) i.t. Bleo and i.p. injections of saline (Bleo-Sal); (3) i.t. saline and i.p. Sur (Sal-Sur); and (4) i.t. and i.p. saline (Sal-Sal). Animals were sacrificed 14 days after i.t. treatment. Lung injury was evaluated by analysis of bronchoalveolar lavage (BAL) fluid, histologically by the semiquantitative morphological index, and biochemically by analysis of lung hydroxyproline content. In vitro, Sur did not affect TGF-beta induced increase of alpha1 (I) collagen mRNA in human lung fibroblasts. In vivo treatment of mice with Sur did not affect Bleo-induced lung injury. These results indicate that despite its potential anti TGF-beta and lymphocytotoxic effects, Sur is not a therapeutic candidate drug for rescue of lung fibrosis.
Life Sciences 11/2000; 67(23):2873-81. · 2.53 Impact Factor
-
Clinical Radiology 06/2000; 55(5):405-6. · 1.95 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Central nervous system (CNS) involvement is common in hematooncologic diseases. The aim of the current study was to determine the diagnostic value of cerebrospinal fluid (CSF) lactate dehydrogenase (LDH) isoenzyme analysis for the diagnosis of CNS involvement in hematooncologic patients.
The study was comprised of 63 consecutive hematooncologic patients without previous CNS disease who underwent CSF examination as an integral part of their initial staging procedures (44 patients) or for the evaluation of neurologic symptoms (19 patients). Fifteen of these patients had CNS involvement by leukemia or lymphoma. The LDH isoenzyme pattern was established in the CSF of all patients and analyzed by the classification and regression trees (CART) method to construct a decision tree for the prediction of CNS involvement. An additional group of 30 consecutive patients comprised a validation set that was used for cross-validation of the CART-derived decision tree.
A decision tree, with a single split at LDH5 >/= 2.8% for the prediction of CNS involvement, was constructed and validated by data from a validation set of patients. The decision tree had a sensitivity of 93% and a negative predictive value of 98%. One patient (1.6%) and 2 patients (6.6%) were misclassified in the derivation and validation sets, respectively. Overall, in the combined derivation and validation patient population, the decision tree misclassified 3.2% of patients, whereas CSF cytologic examination misclassified 4.3% of patients.
Analysis of the LDH isoenzyme pattern in CSF fluid may be helpful in the evaluation of CNS involvement in patients with hematologic malignancies. The combination of CSF cytology and LDH isoenzyme analysis may improve the sensitivity of CSF cytology significantly.
Cancer 04/2000; 88(7):1599-604. · 4.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We have evaluated the effect of enoxaparin, a potent antithrombotic drug, on bleomycin (Bleo)-induced pulmonary inflammation in mice. Pulmonary injury was induced by a single intratracheal (i.t.) instillation of Bleo. Four groups of female C57BL/6 mice, each received one of four treatments: (1) i.t. Bleo and daily intraperitoneal (i.p.) injections of enoxaparin (EN) starting one day before i.t. instillation of Bleo (Bleo-EN); (2) i.t. Bleo and i.p. injections of saline (Bleo-Sal); (3) i.t. saline and i.p. enoxaparin (Sal-EN); (4) i.t. saline and i.p. saline (Sal-Sal). Animals were sacrificed 14 days after i.t. treatment. Lung injury was evaluated by analysis of bronchoalveolar lavage fluid and histologically by an overall semiquantitative index of lung injury and a quantitative image analysis assessing alveolar wall area fraction and fibrosis fraction. Treatment of mice with enoxaparin did not ameliorate Bleo-induced lung injury. Our study does not establish a critical role of procoagulant activity in the evolution of Bleo-induced lung injury and does not support the use of antithrombotic therapy for the prevention of pulmonary fibrosis.
Experimental Lung Research 10/1999; 25(6):531-41. · 1.22 Impact Factor
-
Postgraduate Medical Journal 06/1999; 75(883):309-12. · 1.94 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study aimed to evaluate the utility of the pleural fluid lactate dehydrogenase (LDH) isoenzyme algorithm for the differential diagnosis of pleural fluid in patients with haematological malignancies. Twenty consecutive haemato-oncological patients with pleural effusion, hospitalized in the Haematology Department during a 2.75-year period, were prospectively and independently evaluated for the cause of effusion by standard methods for the LDH isoenzyme algorithm. The causes of the pleural effusions established during the standard evaluations were compared to the results obtained from the LDH isoenzyme algorithm. Following the standard evaluation, the pleural effusion was attributed to congestive heart failure in one patient, to infection in six, to the underlying malignancy in 12 and to concomitant congestive heart failure and malignancy in one. LDH isoenzyme analysis correctly predicted the cause of pleural effusion in 18 patients (positive predictive value 90%). In haemato-oncological patients, the pleural fluid LDH isoenzyme pattern may be helpful in the differential diagnosis of the most common causes of pleural effusion.
Respiratory Medicine 06/1999; 93(5):338-41. · 2.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The prognosis of patients with refractory or relapsing non-Hodgkin's lymphoma (NHL) after primary therapy is poor and multi-drug salvage treatments are associated with less than 60% response rates, usually of short duration. Here we report the results of a phase II study using a fludarabine-cyclophosphamide (FAMP-Cy) combination as a salvage failure regimen in refractory and relapsing low-grade (6) and intermediate-grade (9) NHL patients. Fifteen patients, who had received up to 4 regimens prior to therapy with FAMP-Cy were treated with fludarabine (25 mg/m2) and cyclophosphamide (300 mg/m2) for 3 consecutive days followed by G-CSF (5 microg/kg). The overall response was 74%, 4 achieving complete responses (CR) and 7 partial responses (PR). All patients with low-grade NHL responded (4 CR, 2 PR); 5 patients with intermediate-grade NHL achieved PR lasting for a median of 5 months. The main toxicity encountered was moderate myelosuppression. Three patients had febrile neutropenia, one had drug-induced fever and a single patient developed severe neurotoxicity. Opportunistic infections due to lymphopenia were not seen. The combination of fludarabine and cyclophosphamide used as a salvage regimen showed an impressive response in a small group of heavily pretreated low-grade NHL patients who had previously received a large number of prior regimens. FAMP-Cy had limited effect in a similar group of intermediate-grade NHL patients. Results with this "failure" regimen are encouraging, however further studies are needed in order to confirm these observations in a larger series of patients.
Leukemia and Lymphoma 04/1999; 33(1-2):155-60. · 2.58 Impact Factor
-
Annals of Pharmacotherapy 03/1999; 33(2):253-4. · 2.13 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The role of lymphocytes and their subpopulations in lung fibrosis is as yet unclear.
To define the role of immunomodulation in bleomycin-induced inflammatory fibrotic lung injury, by testing the effect of two known Th1 inhibitors: linomide and pentoxifylline.
C57BL/6 mice were treated by a single intratracheal instillation of 0.06 mg bleomycin in 0.01 ml saline or saline alone. Treatment groups included: (1) intratracheal bleomycin and daily treatment with linomide or pentoxifylline; (2) intratracheal bleomycin and daily water; (3) intratracheal saline and daily linomide or pentoxifylline; (4) intratracheal saline and daily water. Linomide and pentoxifylline were available per os in the drinking water from 1 day prior to intratracheal instillation. Animals were studied 14 days after intratracheal instillation. Lung injury was evaluated by total and differential cell count in bronchoalveolar lavage fluid, by a semiquantitative morphological index of lung injury and a quantitative image analysis of cellularity, fibrosis fraction and alveolar wall area fraction, and by biochemical analysis of lung hydroxyproline content.
Linomide or pentoxifylline did not cause any lung injury in saline-treated control mice. Overt signs of lung injury were apparent in bleomycin-treated mice. These changes were not affected by daily treatment with linomide or pentoxifylline, which were given in the highest tolerable dose.
This study does not support the use of linomide or pentoxifylline to prevent or ameliorate lung fibrosis and may suggest that drug-induced differentiation of T lymphocytes into Th1/th2 subpopulations does not affect the evolution of bleomycin-induced lung injury.
Respiration 02/1999; 66(5):455-62. · 2.26 Impact Factor
-
Acta Haematologica 02/1999; 101(3):161-2. · 1.35 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A novel and as yet unrecorded translocation, (1;2)(p34;p21-22), detected in a patient with acute myeloid leukemia (AML) is reported. The leukemia--in this case, AML-M4--showed a rapidly progressive fatal course despite an early transient response to aggressive chemotherapy. In this patient, the leukemic cells showed a novel balanced translocation, (1;2)(p34;p21-22), in most of the metaphases at the time of diagnosis and during subsequent relapse. Interferon-inducible double-stranded RNA-dependent protein kinase (ds RNA-PK) is located in the chromosome region, 2p21-22, that was involved in the translocation in this case. The possible role of ds RNA-PK in leukemogenesis is briefly mentioned.
Cancer Genetics and Cytogenetics 11/1998; 106(1):78-9. · 1.39 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Eleven cases (6 adults and 5 pediatrics) of shoulder septic arthritis are described, and the English literature from 1960 to 1997 reviewed, for a total of 168 cases. Shoulder septic arthritis is an uncommon and difficult diagnosis requiring a high index of suspicion and early evaluation of the affected shoulder by the clinician. The disease usually involves very young infants or elderly patients (65-75 years old). Associated medical conditions were identified in 60% of the patients and include systemic disorders such as liver diseases, alcoholism, and malignancies in 46%; preceding chronic arthritic disorders in 24%; and associated infectious focus in 13% of the patients. Associated infections were more prevalent in the pediatric population. Intravenous drug abuse appears not to constitute a major risk factor; it was identified in less than 5% of patients. All patients presented with acute shoulder ache or with exacerbation of existing chronic pain in joints previously damaged. Elevated body temperature (over 38 degrees C) appeared in 67% of the adult patients and in over 90% of the pediatric patients. Shoulder arthritis was frequently accompanied by an accelerated erythrocyte sedimentation rate that may rise above 100 mm/hr. Increased white blood cell count was found in approximately 40% of patients. The initial X-rays were frequently normal, while ultrasonography supported the diagnosis in some cases by demonstrating accumulation of fluid inside the joint space. Aspiration of synovial fluid from the affected glenohumeral joint was necessary to evaluate the offending pathogen. False-negative Gram stain appeared in approximately 90% of the patients, whereas synovial fluid cultures demonstrated the pathogen in 88% of patients. Blood cultures were positive in 50% of adult patients and 90% of pediatric patients. The most common isolated pathogen was Staphylococcus aureus, which accounted for 41% of infections. Gram-negative bacilli, which accounted for about 20% of infections, are more prevalent in the pediatric population, especially the neonates. Pyogenic shoulder arthritis should first be treated with intravenous antibiotics, effective at least against staphylococcal infections, until the organisms and sensitivities are identified. Duration of antibiotic therapy should be 3-6 weeks. Unfortunately, our experience in addition to the literature summary does not allow statistical analysis and firm conclusions concerning the best therapeutic approach. However, it appears that in the adult population an operative draining procedure is preferred, whereas in the pediatric population, a closed needle aspiration, if needed at all, is the optimal treatment. With prompt antibiotic therapy and drainage of the shoulder, the patient can be expected to improve clinically, with no serious long-term debilitating effects from the disease.
Medicine 06/1998; 77(3):177-87. · 4.35 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Intravascular lymphomatosis (IVL) is a rare malignancy characterized by neoplastic proliferation of lymphoid cells within the lumens of arteries, small veins and capillaries. We report four patients with IVL and review the recent world literature, relating to incidence, clinical features and possible therapy. In these cases diagnosis was established coincidentally in one patient after prostatectomy. This patient eventually had central nervous system involvement. In two other patients IVL was diagnosed from skin lesions. In the fourth case the diagnosis was established at post-mortem examination, where involvement of most organs was evident but particularly kidneys, myocardium, gastrointestinal tract and lymph nodes. Therapy was given to three patients, but the disease progressed in two and they both died with evidence of central nervous system involvement, while the third patient has had a good partial response to combination chemotherapy but has relapsed within two months of completing chemotherapy. As evident from our patients and the literature review IVL has a variable clinical course and currently, there appears to be no effective therapy for this rare disorder.
Leukemia and Lymphoma 06/1998; 29(5-6):585-93. · 2.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This prospective study was designed to explore the prevalence and the clinical and prognostic significance of anticardiolipin (ACL) antibodies in patients with acute myeloid leukemia (AML). The study includes 37 consecutive AML patients >15 years old without previous history of thromboembolism, recurrent fetal loss, or autoimmune disease and with no evidence of infection at the time of enrollment. ACL antibodies were found in 25 patients (68%). None of the patients had high positive titers; 8 had moderately positive while 17 had low positive ACL antibody titers. ACL antibody positivity did not predict response to chemotherapy and was not correlated with age, gender, FAB class, platelet and white blood cell counts at presentation, and the risk of thromboembolism. ACL antibody titers did correlate, however, with AML activity in the majority of patients (93%) during 4-19 months of follow up. These results demonstrate a high prevalence of ACL antibodies in AML patients and suggest that serum ACL antibodies may be a useful adjunct in predicting relapse and documenting disease activity and therapy response.
American Journal of Hematology 02/1998; 57(2):139-43. · 4.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Trichosporon beigelli is an uncommon but frequently fatal invasive fungal infection in immunosupressed patients. We report on a patient with acute myeloid leukemia who developed splenic calcifications following Trichosporon beigelli infection.
European Radiology 02/1998; 8(6):922-4. · 3.22 Impact Factor
-
M Glazer,
R Breuer,
N Berkman, I S Lossos,
J Kapelushnik,
A Nagler,
E Naparstek,
M R Kramer,
J Lafair,
D Engelhard,
R Or
[show abstract]
[hide abstract]
ABSTRACT: Bone marrow transplantation (BMT) has become the therapy of choice for a number of malignant and nonmalignant hematologic and nonhematologic disorders. A frequent complication after BMT is pulmonary disease which is associated with a high mortality rate. We examined the results of 79 bronchoscopies performed between May 1991 and May 1995 in 62 patients for the evaluation of pulmonary complications after BMT. In all cases bronchoalveolar lavage (BAL) was performed, in 10% transbronchial biopsy (TBB) was also carried out and in 13% bronchoscopy was followed by open lung biopsy. Positive results were found in 67% of bronchoscopies. Fungal infection (Candida and Aspergillus species) was the most common finding (18%), bacterial infection was found in 13%, mixed (fungal and bacterial) infection in 6%, cytomegalovirus in 11% and Pneumocystis carinii pneumonia in 4%. Diffuse alveolar hemorrhage was detected in 11% of cases. Idiopathic pneumonia syndrome (IPS) was diagnosed by TBB in 3% of procedures. We conclude that BAL is a safe and accurate procedure for the evaluation of pulmonary complications after BMT. TBB should be considered in the absence of thrombocytopenia for the diagnosis of IPS. If bronchoscopy findings are negative, open lung biopsy should be considered.
Acta Haematologica 02/1998; 99(1):22-6. · 1.35 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The role of lymphocytes in bleomycin (Bleo)-induced lung injury remains obscure. In normal hamsters, peribronchial lymphatic tissue (PBLT) has been found to contain a large population of T lymphocytes responsive to interleukin 2 (IL-2) but not to IL-4. Lung injury induced by a single intratracheal instillation of Bleo in hamsters has been ameliorated by cyclosporin A (CyA). In the present study, using this model, PBLT-derived lymphocyte function was explored for 28 days after Bleo instillation. Increase in PBLT lymphocytes occurred at five time points investigated, reaching highest values on day +7 (p < 0.0025). Cell proliferation in response to concanavalin A was enhanced, while IL-2 +/- the mitogen had no effect. In contrast to its inactivity in the normal hamster, in the Bleo-injured animal IL-4 alone induced T cell proliferation (p = 0.0077) on day +7. CyA therapy initially suppressed and delayed recovery of the number of lymphocytes and their activation. The results of this study suggest the existence of a vulnerable period in Bleo-induced lung injury and indicate that lymphocytes participate in the pathogenesis of the insult to the tissue. The unresponsiveness to IL-2 and the emergence of cellular response to IL-4 indicate immune deviation in PBLT-derived T cells.
Life Sciences 01/1998; 63(13):1183-93. · 2.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A case of Candida abscess of the thyroid in a patient with acute lymphoblastic leukemia is described. The patient developed this rare complication after treatment with steroids and combination chemotherapy, during therapy with broad spectrum antibiotics for febrile neutropenia. Prior to the thyroiditis the patient had pulmonary aspergillosis. The abscess developed during treatment with high dose Amphotericin B. Unlike previous cases, the Candida was isolated to the thyroid, with no evidence of Candidemia or Candida infection in other sites.
European journal of medical research 09/1997; 2(8):365-6. · 1.13 Impact Factor
