ABSTRACT
INTRODUCTION: Unfractionated heparin (UFH), low molecular weight heparin or fondaparinux are recommended for venous thromboembolism (VTE) prophylaxis in acutely ill medical patients. There are limited data on the safety of fondaparinux for VTE prophylaxis in ischemic stroke. We examined adverse event frequency in hospitalized patients with ischemic stroke who received VTE prophylaxis with fondaparinux versus UFH. MATERIALS AND METHODS: We performed a propensity score matched analysis on a retrospective cohort of 644 consecutive patients with acute ischemic stroke receiving fondaparinux (n=322) or UFH (n=322) for VTE prophylaxis. Patients who received intravenous tPA and continuous intravenous infusions of UFH were excluded. The primary outcome was major hemorrhage (intracranial or extracranial) and the secondary outcome was total hemorrhage (major and minor hemorrhage) during hospitalization. We also examined the rate of symptomatic VTE. RESULTS: Mean age of the matched cohort was 71.3±14.1 years, median NIHSS score was 4 (IQR 1-11), median duration of anticoagulant exposure was 5 (IQR 3-8) days, and 98.1% received antiplatelet medications. In the matched cohort, there were less observed major hemorrhages in the fondaparinux group 1.2% (4/322) compared to UFH 3.7% (12/322), but this difference was not significant (OR=0.33, 95% CI 0.08-1.10, p=0.08). There were also no significant differences in total hemorrhage (p=0.15), intracranial hemorrhage (p=0.48), major extracranial hemorrhage (p=0.18) and symptomatic VTE (p=1.00) between the groups. CONCLUSIONS: Fondaparinux is not associated with increased hemorrhagic complications compared with UFH in patients with ischemic stroke. There were low rates of symptomatic VTE in both groups.
Subject(s)
Anticoagulants/therapeutic use , Heparin/therapeutic use , Polysaccharides/therapeutic use , Stroke/drug therapy , Venous Thromboembolism/prevention & control , Aged , Cohort Studies , Female , Fondaparinux , Humans , Male , Retrospective Studies , Venous Thromboembolism/drug therapyABSTRACT
The uptake in Europe of Energy from Waste (EfW) incinerator plants has increased rapidly in recent years. In the UK, 25 municipal waste incinerators with energy recovery are now in operation; however, their waste supply chains and business practices vary significantly. With over a hundred more plant developments being considered it is important to establish best business practices for ensuring efficient environmental and operational performance. By reviewing the 25 plants we identify four suitable case study plants to compare technologies (moving grate, fluidised bed and rotary kiln), plant economics and operations. Using data collected from annual reports and through interviews and site visits we provide recommendations for improving the supply chain for waste incinerators and highlight the current issues and challenges faced by the industry. We find that plants using moving grate have a high availability of 87-92%. However, compared to the fluidised bed and rotary kiln, quantities of bottom ash and emissions of hydrogen chloride and carbon monoxide are high. The uptake of integrated recycling practices, combined heat and power, and post incineration non-ferrous metal collections needs to be increased among EfW incinerators in the UK. We conclude that one of the major difficulties encountered by waste facilities is the appropriate selection of technology, capacity, site, waste suppliers and heat consumers. This study will be of particular value to EfW plant developers, government authorities and researchers working within the sector of waste management.
Subject(s)
Incineration/standards , Incineration/instrumentation , United KingdomABSTRACT
Tedera (Bituminaria bituminosa (L.) C.H. Stirton var. albomarginata) has been successfully established across the mixed-farming (wheat-sheep) region of Western Australia because this species has remarkable drought tolerance and can survive the dry-summer period with strong retention of green leaf. A leaf spot symptom involving pale brown lesions with distinct dark brown margins had been observed in genetic evaluation plots of tedera at Medina and Mount Barker, Western Australia, and a Phoma sp. was isolated. Single-spore isolations of a typical Phoma sp. isolate were made onto potato dextrose agar and maintained at 20°C, and a representative culture has been lodged in the Western Australian Culture Collection Herbarium maintained at the Department of Agriculture and Food Western Australia (Accession No. WAC13435). Amplification of the internal transcribed spacer (ITS) 1 and ITS2 regions flanking the 5.8S rRNA gene were carried out with universal primers ITS1 and ITS4 according to published protocol (3). The DNA PCR products were sequenced and BLAST analyses was used to compare sequences with those in GenBank. The sequence had 99% nucleotide identity with the corresponding sequence in GenBank for Phoma herbarum. Isolates also showed morphological (e.g., 1) and molecular (e.g., 2) similarities with P. herbarum as described in other reports. The relevant sequence information for a representative isolate has been lodged in GenBank (Accession No. JQ282910). A conidial suspension of 107 conidia ml-1 from a single-spore culture was spray inoculated onto foliage of 6-week-old tedera plants maintained under >90% relative humidity conditions for 72-h postinoculation. Symptoms evident by 10 days postinoculation consisted of pale brown lesions, mostly 1.5 to 4 mm in diameter, which developed a distinct, dark brown margin. Occasional lesions also showed a distinct chlorotic halo extending 1 to 1.5 mm outside the boundary of the lesion. Infection studies were successfully repeated twice and P. herbarum was readily reisolated from infected foliage. No disease was observed on and no P. herbarum were isolated from water-inoculated control plants. Except for a recent published report of P. herbarum on field pea (Pisum sativum L.) (2), this pathogen has only been noted in the Australian Plant Pest Database as occurring on lucerne (Medicago sativa L.) and soybean (Glycine max (L.) Merr.) in Western Australia in 1985 and on a Protea sp. in 1991. To our knowledge, this is the first published report of P. herbarum as a pathogen on tedera in Australia or elsewhere. That P. herbarum occurs on other hosts in Australia and has a wide host range elsewhere together suggest its potential to be a pathogen on a wider range of host genera and species. References: (1) G. L. Kinsey. No. 1501 in: IMI Descriptions of Fungi and Bacteria. 2002. (2) Y. P. Li et al. Plant Dis. 95:1590, 2011. (3) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, CA, 1990.
ABSTRACT
OBJECTIVE: Atrial fibrillation (AF) may be present within a subset of patients with presumed cryptogenic TIA or stroke and remains undetected by standard diagnostic methods. We hypothesized that AF may be an under-recognized mechanism for cryptogenic TIA/stroke. METHODS: A consecutive series of 56 patients with cryptogenic TIA/stroke was analyzed after diagnostic evaluation and Mobile Cardiac Outpatient Telemetry (MCOT) for up to 21 days. Demographic, radiographic, echocardiographic, and MCOT results were reviewed. Predictors of AF detection by MCOT were determined by univariate analysis including Student t test and Fisher exact tests and multivariate analysis. RESULTS: The median MCOT monitoring duration was 21 (range 5-21) days resulting in an AF detection rate of 23% (13/56). AF was first detected after a median of 7 (range 2-19) days of monitoring. Twenty-seven asymptomatic AF episodes were detected in the 13 patients, of which 85% (23/27) were <30 seconds and the remaining 15% (4/27) were 4-24 hours in duration. Diabetes was predictive of AF detection by both univariate (p = 0.024) and multivariate analysis (OR 6.15; 95% CI 1.16 to 32.73; p = 0.033). CONCLUSIONS: There is a high rate of atrial fibrillation (AF) detection by Mobile Cardiac Outpatient Telemetry (21 days) in patients with cryptogenic TIA/stroke that may be related to extended monitoring duration, patient selection, and inclusion of all new onset AF episodes. Brief AF episodes (<30 seconds) may be biomarkers of more prolonged and clinically significant AF.
Subject(s)
Atrial Fibrillation/diagnosis , Ischemic Attack, Transient/complications , Stroke/complications , Telemetry/methods , Aged , Analysis of Variance , Atrial Fibrillation/etiology , Atrial Fibrillation/physiopathology , Echocardiography/methods , Female , Humans , Logistic Models , Male , Middle Aged , Monitoring, Physiologic , Outpatients , Retrospective StudiesABSTRACT
Normal turnover of T lymphocytes is slow relative to other blood cells. Consequently, the physical removal of circulating leucocytes by thoracic duct drainage, repeated leukapheresis or blood filtration results in T cell depletion and immunosuppression. However, clinical use of such procedures is impractical compared with immunosuppressive drugs or radiation. None the less, immunosuppression by physical depletion of T cells, avoiding the systemic toxicities of drugs and radiation, might have clinical advantages if immunophenotypically distinct T cell subsets could be depleted selectively. Recent advances in targeted plasma protein apheresis using adsorbent macrobead columns prompted us to determine whether analogous techniques might permit CD4+ T lymphocytes to be removed selectively from whole blood. To explore this possibility, we linked murine anti-human-CD4 and isotype-identical control monoclonal antibodies (mAbs) to agarose, polyacrylamide and polystyrene macrobeads (150-350 microm) and then evaluated the selectivity, specificity and efficiency of macrobead columns to remove CD4+ T cells from anti-coagulated whole blood at varying mAb densities and flow rates. We also examined saturation kinetics and Fc-oriention versus random coupling of mAbs to macrobeads. Sepharose 6MB macrobead (250-350 microm) columns proved to be most effective, selectively removing up to 98% of CD4+ T cells from whole blood. Moreover, depletion efficiency and selectivity were retained when these columns were reused after elution of adherent CD4+ cells. These studies indicate that selective depletion of T lymphocyte subsets by whole blood immunoadsorption apheresis using mAb-linked macrobead columns may be feasible on a clinical scale. It is possible that such apheresis techniques could achieve targeted forms of immunosuppression not possible with drugs or radiation.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , Leukapheresis/methods , Lymphocyte Depletion/methods , Acrylic Resins , Animals , Antibodies, Monoclonal/immunology , CD4 Lymphocyte Count , Feasibility Studies , Leukapheresis/instrumentation , Lymphocyte Depletion/instrumentation , Mice , Polystyrenes , Sepharose/analogs & derivativesABSTRACT
Clinical outcomes of patients with AL amyloidosis treated with high-dose melphalan and stem cell transplantation (HDM/SCT) are tightly linked to the achievement of a hematologic complete response (HCR). We conducted a prospective trial to determine whether a second cycle of HDM/SCT could induce HCR in patients in whom the plasma cell dyscrasia persisted following initial treatment with HDM/SCT. Sixty-two patients were enrolled. Nine patients (15%) were removed from the protocol. Of the 53 patients continuing in this study, four died within 100 days of treatment (8%), and 27 (55%) achieved an HCR at 6 months after the first cycle of HDM/SCT. Of the 22 patients who did not achieve an HCR after initial treatment, 17 received a second HDM/SCT, 1 died within 100 days of treatment (6%), while 5 (31%) achieved an HCR. Thus, the HCR rate was 67% (32/48) for surviving patients on study, 60% (32/53) for all patients who received initial cycle of HDM/SCT, and 56% (35/62) by intention-to-treat. The median survival for all patients enrolled on the trial has not yet been reached. Thus, tandem cycles of HDM/SCT can increase the proportion of patients who achieve an HCR.
Subject(s)
Amyloidosis/drug therapy , Antineoplastic Agents, Alkylating/administration & dosage , Hematopoietic Stem Cell Transplantation , Immunoglobulin Light Chains , Melphalan/administration & dosage , Adult , Aged , Amyloidosis/mortality , Amyloidosis/therapy , Antineoplastic Agents, Alkylating/adverse effects , Combined Modality Therapy , Female , Hematopoietic Stem Cell Transplantation/mortality , Humans , Male , Melphalan/adverse effects , Middle Aged , Patient Dropouts , Prospective Studies , Survival Rate , Transplantation, Autologous , Treatment OutcomeABSTRACT
Light chain deposition disease (LCDD) is caused by a clonal plasma cell disorder in which fragments of monoclonal immunoglobulin light chains form non-fibrillary deposits in various tissues resulting in organ dysfunction. Crystal storing histiocytosis (CSH) is another light chain deposition disorder in which monoclonal light chains form intracytoplasmic crystals. Both are uncommon diseases for which there is limited treatment experience. Between 2003 and 2005, five patients with LCDD and one with CSH were treated at Boston University Medical Center with high-dose melphalan and autologous peripheral blood stem cell transplantation (HDM/SCT). Five of the six patients had predominantly renal involvement, and one patient with LCDD had biopsy-proven deposits in the myocardium. Molecular characterization revealed that the pathologic light chains were kappa in four of the six patients, and sequence analysis revealed unusual germline donor genes and high rates of amino-acid substitutions. One light chain sequence encoded a new potential N-linked glycosylation site, and another showed evidence of antigen selection. All patients are alive and five of the six patients are in complete hematologic remission at a median follow-up of 12 months (range 4-29 months) after HDM/SCT. In our experience, HDM/SCT is a feasible and effective treatment approach for these disorders.
Subject(s)
Immunoglobulin kappa-Chains/metabolism , Immunoglobulin lambda-Chains/metabolism , Kidney Diseases/therapy , Melphalan/therapeutic use , Stem Cell Transplantation , Adult , Histiocytosis/therapy , Humans , Male , Melphalan/administration & dosage , Middle Aged , Transplantation, Autologous , Treatment OutcomeABSTRACT
AL amyloidosis, a systemic disorder characterized by widespread deposition of amyloid fibrils derived from monoclonal Ig light chains in organs and soft tissues, is typically caused by an underlying plasma cell dyscrasia. However, this disease can also be associated rarely with a B-cell lymphoproliferative disorder. In this report, we describe the presentation and clinical course of 16 patients with this association. Although amyloid-related organ involvement in these patients was typical of AL amyloidosis, the patients in this series were on average older and more likely to be female than patients with disease associated with a plasma cell dyscrasia. They were also more likely to have multisystem involvement. Treatment decisions were based primarily on the dominent hematopathologic features of the associated lymphoproliferative disorder. However, high-dose melphalan and stem cell transplantation was the primary therapy in 5 patients, and each of these patients had prolonged survival, ranging from 36 to 102 months.
Subject(s)
Amyloidosis , B-Lymphocytes/pathology , Bone Marrow Cells/pathology , Paraproteinemias , Adult , Aged , Aged, 80 and over , Amyloidosis/mortality , Amyloidosis/pathology , Amyloidosis/therapy , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Alkylating/therapeutic use , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Male , Melphalan/administration & dosage , Melphalan/therapeutic use , Middle Aged , Paraproteinemias/mortality , Paraproteinemias/pathology , Paraproteinemias/therapy , Peripheral Blood Stem Cell Transplantation , Radiotherapy , Treatment OutcomeABSTRACT
Serum free light-chain (FLC) concentrations were measured by a sensitive nephelometric immunoassay in 66 patients with AL amyloidosis before and after treatment with high-dose melphalan and autologous stem cell transplantation (HDM/SCT). At 1 year after HDM/SCT, 27 patients (41%) achieved a complete hematologic response (CR), that is, disappearance of the monoclonal gammopathy previously evident by immunofixation electrophoresis (IFE) in serum and urine and of plasma cell clonality in the bone marrow. Abnormally elevated FLC levels became normal in 27 patients (41%), and decreased by >90% in 37 (56%). Average improvements in FLC were 94% for patients who achieved a CR and 72% for those who did not (P=0.0001). However, a reduction in FLC of >90% was associated with a similar high likelihood of clinical improvement and prolonged survival, whether or not patients achieved a CR. While CR, as defined by standard criteria, is a more stringent indicator of hematologic response than are decreases in abnormally elevated FLC levels per se, these measures of hematologic response are complementary, and decreases in FLC are more readily detected early after treatment than are the changes in IFE and marrow studies required to determine CR.
Subject(s)
Amyloidosis/therapy , Melphalan/therapeutic use , Stem Cell Transplantation/methods , Transplantation, Autologous/methods , Adult , Aged , Amyloid/chemistry , Amyloid/metabolism , Bone Marrow/pathology , Culture Media, Serum-Free/pharmacology , Disease-Free Survival , Female , Humans , Immunoassay , Immunoelectrophoresis/methods , Immunohistochemistry , Male , Middle Aged , Paraproteinemias/diagnosis , Remission Induction , Retrospective Studies , Time Factors , Treatment OutcomeABSTRACT
Treatment of patients with AL amyloidosis with high-dose melphalan and autologous peripheral blood stem cells (PBSC) produces hematologic remissions in approximately 40% of evaluable patients, accompanied by improvements in organ disease and quality of life. These patients, who frequently have amyloid deposits in bone marrow blood vessels and interstitium and impaired function of kidneys, liver, spleen, and heart, represent an unusual population for stem cell transplantation, with unique problems. To identify factors influencing engraftment rates after chemotherapy and autologous granulocyte colony-stimulating factor (G-CSF)-mobilized PBSC reinfusion, we studied a group of 225 patients. The median time to neutrophil engraftment was 10 days (range, 8-17 days). In a multivariate analysis, the factors positively affecting the rate of neutrophil engraftment were CD34+ stem cell dose, female gender, and minimal prior alkylator therapy. The median time to platelet engraftment was 13 days (range, 7-52 days). Factors positively affecting platelet engraftment, in addition to CD34+ cell dose, included preserved renal function and the absence of neutropenic fever. The conditioning dose of intravenous melphalan was not found to be an independent predictive factor for hematopoietic recovery. Thus, in this patient population, organ function and host and hematopoietic factors influence engraftment after PBSC rescue.
Subject(s)
Amyloidosis/therapy , Graft Survival , Peripheral Blood Stem Cell Transplantation/methods , Predictive Value of Tests , Adult , Aged , Aged, 80 and over , Antigens, CD34 , Antineoplastic Agents, Alkylating , Blood Platelets/physiology , Female , Fever , Humans , Kinetics , Male , Melphalan/administration & dosage , Middle Aged , Neutrophils/physiology , Proportional Hazards Models , Retrospective Studies , Sex Factors , Transplantation, AutologousABSTRACT
SUMMARY: A prospective randomized trial was conducted to study the timing of high-dose intravenous melphalan and autologous stem cell transplantation (HDM/SCT) in AL amyloidosis. In all, 100 newly diagnosed patients were randomized to receive HDM/SCT, either as initial therapy (Arm-1) or following two cycles of oral melphalan and prednisone (Arm-2). The objectives of the trial were to compare survival and hematologic and clinical responses. With a median follow-up of 45 months (range 24-70), the overall survival was not significantly different between the two treatment arms (P=0.39). The hematologic response and organ system improvements after treatment did not differ between the two groups. Fewer patients received HDM/SCT in Arm-2 because of disease progression during the oral chemotherapy phase of the study, rendering them ineligible for subsequent high-dose therapy. This affected patients with cardiac involvement particularly, and led to a trend for an early survival disadvantage in Arm-2. Hence, newly diagnosed patients with AL amyloidosis eligible for HDM/SCT did not benefit from initial treatment with oral melphalan and prednisone, and there was a survival disadvantage for patients with cardiac involvement if HDM/SCT was delayed by initial oral chemotherapy.
Subject(s)
Amyloidosis/therapy , Hematopoietic Stem Cell Transplantation/methods , Melphalan/administration & dosage , Amyloidosis/mortality , Amyloidosis/pathology , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Alkylating/toxicity , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/toxicity , Female , Heart Diseases/therapy , Hematopoietic Stem Cell Transplantation/mortality , Humans , Kidney Diseases/therapy , Leukapheresis , Male , Melphalan/toxicity , Middle Aged , Prednisone/administration & dosage , Survival Analysis , Transplantation, Autologous , Treatment OutcomeABSTRACT
The frequency of splenic involvement in AL amyloidosis is not precisely known. However, splenomegaly has been reported in 4-13% of patients. We report four cases of spontaneous splenic rupture in patients with AL amyloidosis. Splenic rupture was the initial manifestation of the disease in one of these patients. The other three experienced splenic rupture during or after high-dose intravenous melphalan with autologous peripheral blood stem cell transplantation (HDM/SCT): one during stem cell mobilization with G-CSF prior to HDM/SCT and two after hematopoietic recovery following treatment. Two of the four patients had Factor X deficiency, the most common coagulation abnormality associated with AL amyloidosis. All four patients underwent splenectomy without significant postoperative complications. Splenic rupture in AL amyloidosis as a complication of aggressive treatment with HDM/SCT has not been reported previously.
Subject(s)
Amyloidosis/complications , Spleen/injuries , Factor X Deficiency/complications , Female , Humans , Male , Middle Aged , Rupture, Spontaneous/etiologyABSTRACT
There is evidence that acquired dysfunction of neutrophils, monocytes, or macrophages is an important cause of infection in patients with diabetes mellitus, renal or hepatic failure, alcoholism, autoimmune diseases, influenza or human immunodeficiency virus infection, burns, and trauma. Distinguishable mechanisms of acquired phagocyte dysfunction include inhibitory effects of metabolic disturbances (e.g., hyperglycemia, uremia), chemical toxins (e.g., ethanol), viral proteins on phagocyte activation, and pathologic activation of phagocytes in the circulation (e.g., after hemodialysis, burns, or cardiopulmonary bypass). Although the burden of morbidity and mortality resulting from acquired phagocyte dysfunction appears to be vast, research in this area has been hampered by the complexity of the underlying illnesses and by limitations of laboratory assays and clinical study methodology. Given the advent of improved assays of phagocyte functions and treatments that can enhance these functions, there is a pressing need for more prospective studies of acquired phagocyte dysfunction.
Subject(s)
Metabolic Diseases/etiology , Phagocyte Bactericidal Dysfunction/complications , Alcoholism/etiology , Autoimmune Diseases/etiology , Burns/etiology , Diabetes Mellitus/etiology , HIV , Humans , Liver Cirrhosis/etiology , Orthomyxoviridae , Renal Insufficiency/etiology , Wounds and Injuries/etiologyABSTRACT
Primary or AL amyloidosis results from a plasma cell dyscrasia in which fibrillar light chain protein deposition leads to organ failure and death. Standard treatment for AL amyloidosis has been oral melphalan and prednisone. However, this form of treatment modifies the natural history of this lethal disease only marginally, extending median survival from 13 months following diagnosis to 17 months. At Boston University Medical Center, we have developed treatment protocols using high-dose intravenous melphalan with autologous peripheral blood stem cell transplantation (HDM/SCT) to treat AL amyloidosis, and we have treated over 200 patients with HDM/SCT during the past six years. This extensive experience has shown that patients with AL amyloidosis, despite multisystem involvement and compromised organ function can tolerate this aggressive form of treatment. Furthermore, HDM/SCT results in durable hematologic responses in a substantial proportion of patients, and such responses are associated with clinical improvement, decreased amyloid-related organ dysfunction, and prolonged survival. However, toxicity from treatment is high (overall peri-transplant mortality, 14%), particularly for those patients with clinically significant cardiac involvement. For this reason, we believe a multidisciplinary management approach is essential when using HDM/SCT for treatment of AL amyloidosis. Based on our experience, we believe that HDM/SCT is the treatment of choice for patients with AL amyloidosis who have a good performance status and limited cardiac involvement at the time of diagnosis. HDM/SCT offers the best chance for hematologic remission, prolongation of survival, and reversal of amyloid-related disease. At the same time, we believe that HDM/SCT should continue to be examined in the context of clinical trials, directed at developing approaches to broaden the applicability of this therapy by minimizing toxicity and to increase the likelihood of complete hematologic responses.
Subject(s)
Alkylating Agents/therapeutic use , Amyloidosis/therapy , Hematopoietic Stem Cell Transplantation , Melphalan/therapeutic use , Academic Medical Centers , Adult , Aged , Aged, 80 and over , Alkylating Agents/administration & dosage , Alkylating Agents/adverse effects , Amyloidosis/complications , Amyloidosis/drug therapy , Amyloidosis/mortality , Amyloidosis/pathology , Boston/epidemiology , Cardiomyopathies/etiology , Cardiomyopathies/pathology , Cardiomyopathies/therapy , Case Management , Clinical Trials as Topic , Combined Modality Therapy , Factor X Deficiency/complications , Factor X Deficiency/therapy , Female , Forecasting , Hematopoietic Stem Cell Mobilization , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/mortality , Humans , Infusions, Intravenous , Male , Melphalan/administration & dosage , Melphalan/adverse effects , Middle Aged , Multicenter Studies as Topic , Multiple Organ Failure/etiology , Multiple Organ Failure/mortality , Nephrotic Syndrome/etiology , Nephrotic Syndrome/therapy , Patient Care Team , Patient Selection , Pilot Projects , Remission Induction , Renal Dialysis , Survival Analysis , Survival Rate , Transplantation Conditioning/methods , Transplantation Conditioning/mortality , Treatment OutcomeABSTRACT
Bone marrow (BM) aspiration and biopsy are used commonly in clinical practice to diagnose invasive tissue infections caused by Mycobacterium avium intracellulare (MAC), Mycobacterium tuberculosis (TB), and Histoplasma capsulatum (HC) in patients with human immunodeficiency virus-1 (HIV) infection. However, the value of these invasive procedures relative to other diagnostic approaches has not been clearly defined. To determine the value of BM culture and BM histology in the diagnosis of opportunistic MAC/TB and HC infections in immunosuppressed patients with HIV, we retrospectively reviewed the records of 56 adult patients with HIV who underwent a single BM aspiration, biopsy, and culture because of unexplained fever and/or other clinical features suggestive of MAC/TB or HC infection. Thirty-two patients (57%) were ultimately diagnosed with MAC/TB or HC infection by positive cultures of BM, blood, sputum, or bronchoalveolar lavage fluid or by the histologic detection of organisms in biopsies of BM or other tissues. The diagnostic sensitivity of BM cultures was equal to that of blood cultures (20/32, or 63%). Granuloma and/or histologically apparent organisms were seen in BM biopsy specimens in 11 of 32 individuals (34%) ultimately diagnosed with MAC/TB or HC infections. Among these 11 cases, both granuloma and acid-fast staining organisms were found in the BM biopsy specimens of 2 individuals for whom both BM and blood cultures were negative. Certain clinical symptoms and signs at the time of BM examination were found by logistic regression analysis to be significantly associated with a subsequent diagnosis of MAC/TB or HC infections; these included high fever, long duration of febrile days prior to BM examination, and elevated direct bilirubin. In conclusion, while the diagnostic sensitivity of BM cultures was found to be no greater than that of blood cultures in detecting MAC/TB or HC infections in immunosuppressed HIV+ patients, histopathologic examination of BM specimens resulted in the relatively rapid identification of nearly one third of infected patients who underwent BM examination, and also identified infections in some patients who were culture negative. These findings support the continued use of BM aspiration, biopsy, and culture for the diagnosis of opportunistic MAC/TB or HC infections in immunosuppressed HIV+ patients, particularly when selected clinical features are present.
Subject(s)
AIDS-Related Opportunistic Infections/diagnosis , Bone Marrow/microbiology , HIV Infections/complications , Histoplasmosis/diagnosis , Mycobacterium Infections/diagnosis , AIDS-Related Opportunistic Infections/microbiology , AIDS-Related Opportunistic Infections/pathology , Adult , Bilirubin/metabolism , Biopsy, Needle , Blood Cells/microbiology , Bone Marrow/pathology , Colony Count, Microbial , Female , Fever/microbiology , HIV Infections/pathology , Histoplasmosis/microbiology , Histoplasmosis/pathology , Humans , Male , Middle Aged , Mycobacterium Infections/microbiology , Mycobacterium Infections/pathology , Predictive Value of Tests , Retrospective StudiesABSTRACT
BACKGROUND: Dose-intensive intravenous melphalan with autologous blood stem-cell transplantation induces remission of the plasma cell dyscrasia in a substantial proportion of patients with AL amyloidosis. The impact of this treatment on associated renal disease is not known. OBJECTIVE: To determine the effect of dose-intensive intravenous melphalan and autologous blood stem-cell transplantation on AL amyloidosis-associated renal disease. DESIGN: Prospective cohort study. SETTING: Academic medical center. PATIENTS: 65 patients with AL amyloidosis and urinary protein excretion greater than 1 g/24 h who received dose-intensive intravenous melphalan and autologous blood stem-cell transplantation between 1 July 1994 and 30 June 1998. MEASUREMENTS: 24-hour urinary protein excretion, serum cholesterol level, serum albumin level, creatinine clearance, urine and serum immunoelectrophoresis, and bone marrow biopsy. Renal response was defined as a greater than 50% reduction in urinary protein excretion in the absence of a 25% or greater reduction in creatinine clearance. Complete hematologic response was defined as absence of detectable monoclonal protein in serum and urine and a bone marrow specimen containing less than 5% plasma cells without clonal dominance of kappa or lambda isotype. RESULTS: Among the 50 patients who survived for at least 12 months, proteinuria, hypoalbuminemia, and hypercholesterolemia improved during follow-up; 36% met criteria for a renal response. Median 24-hour urinary protein excretion decreased from a baseline value of 9.6 g/24 h to 1.6 g/24 h at 12 months among patients with complete hematologic response, and 71% met criteria for a renal response. Twenty-hour urinary protein excretion did not decrease during follow-up among patients with persistent plasma cell disease, and only 11% had a renal response at 12 months (P < 0.001 for hematologic responders vs. nonresponders). CONCLUSION: Dose-intensive intravenous melphalan with autologous blood stem-cell transplantation improves the nephrotic syndrome in patients with AL amyloidosis-associated renal disease. The benefit is largely limited to patients achieving eradication of the underlying plasma cell dyscrasia.
Subject(s)
Amyloidosis/complications , Hematopoietic Stem Cell Transplantation/methods , Melphalan/administration & dosage , Nephrotic Syndrome/complications , Nephrotic Syndrome/therapy , Adult , Aged , Cholesterol/blood , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Hypercholesterolemia/metabolism , Infusions, Intravenous , Male , Melphalan/adverse effects , Middle Aged , Nephrotic Syndrome/metabolism , Proteinuria/prevention & control , Transplantation, Autologous , Treatment OutcomeABSTRACT
Acquired deficiency of factor X occurs in patients with systemic amyloid light-chain (AL) amyloidosis, presumably due to adsorption of factor X to amyloid fibrils. Of 368 consecutive patients with systemic AL amyloidosis evaluated at Boston Medical Center, 32 patients (8.7%) had factor X levels below 50% of normal. Eighteen of these patients (56%) had bleeding complications, which were more frequent and severe in the 12 patients below 25% of normal; 2 episodes were fatal. Ten factor X-deficient patients received high-dose melphalan chemotherapy followed by autologous stem cell transplantation. Of 7 patients alive 1 year after treatment, 4 had a complete hematologic response, and all 4 experienced improvement in their factor X levels. One of 2 additional patients with partial hematologic responses had improvement in factor X. Thus, aggressive treatment of the underlying plasma cell dyscrasia in AL amyloidosis can lead to the amelioration of amyloid-related factor X deficiency.
Subject(s)
Amyloidosis/complications , Factor X Deficiency/etiology , Amyloid , Amyloidosis/epidemiology , Amyloidosis/therapy , Antineoplastic Agents/therapeutic use , Blood Coagulation Tests , Factor X Deficiency/epidemiology , Factor X Deficiency/therapy , Follow-Up Studies , Hematopoietic Stem Cell Transplantation , Hemorrhage/etiology , Incidence , Melphalan/administration & dosage , Transplantation, Autologous , Treatment OutcomeABSTRACT
We prospectively studied absolute lymphocyte (ALC) and monocyte counts (AMC), lymphocyte subsets and proliferative in vitro responses to mitogen and antigen in 12 patients with AL-amyloidosis (AL) undergoing autologous blood stem cell transplantation (SCT) with high-dose i.v. melphalan. Myeloid and lymphoid recovery (>500 per microl) occurred in a median of 10 days post SCT. While there was a continuous decline in the number of CD4+ T cells at 3 months, ALC, AMC, B cells (CD19+), CD8+ T cells, and NK cells (CD16+/56+) returned to baseline. While T cell proliferative responses to phytohemagglutinin (PHA) remained depressed, B cell function measured by the proliferative response to staphylococcal antigen returned to baseline by 3 months. To supplement our findings, we retrospectively evaluated ALC, AMC and serum immunoglobulin levels in a separate group of patients treated with the same protocol at our institution. ALC and AMC recovery was similar to the pattern observed in the initial study group. Immunoglobulin levels remained within normal ranges at 3 and 12 months after SCT. Of 50 patients who were followed for a minimum of 1 year following SCT, seven (14%) developed shingles and one (2%) had PCP pneumonia. In conclusion, cellular immune function, reflected by absolute numbers of CD4+ T cells and PHA responsive T cell proliferation, is significantly suppressed at 3 months after SCT in patients with AL, and this post-transplant immunosuppression is associated with a low but clinically meaningful occurrence of opportunistic infections typical of T cell immunosuppression.
Subject(s)
Amyloidosis/immunology , Amyloidosis/therapy , Hematopoietic Stem Cell Transplantation , Adult , Aged , Amyloidosis/blood , Female , Humans , Immunoglobulins/blood , Lymphocyte Activation , Male , Middle Aged , Prospective Studies , Transplantation, AutologousABSTRACT
The U.S. armed forces deploy active duty personnel to virtually every region of the world. Family members accompany the service member at many of these remote, isolated assignments. This discussion highlights the barriers to the provision of medical care to these active duty personnel, their families, and other eligible beneficiaries, such as government service and Department of Defense civilians. To succeed in this endeavor, the isolated military medical treatment facility must first consider the critical resources available that will enable it to overcome known barriers. Next, careful deliberation will identify the necessary components of a health care network suitable for the remote duty station. The facility must then recognize and address its responsibility to conduct ongoing evaluation of the quality of care and of customer satisfaction with its network. This discussion concludes with a description of a successfully implemented health care network at a remote, isolated duty station.
Subject(s)
Medically Underserved Area , Military Medicine/standards , Military Personnel , Quality Assurance, Health Care/organization & administration , Rural Health , Community Networks/organization & administration , Health Services Accessibility/organization & administration , Humans , International Cooperation , Military Personnel/psychology , Needs Assessment/organization & administration , Patient Satisfaction , United StatesABSTRACT
The incidence of postoperative hydrocephalus and factors relating to it were analyzed in 257 patients undergoing cranial base surgery for tumor resection. A total of 21 (8%) patients developed postoperative hydrocephalus, and all required shunting, Forty-two (17%) patients developed cerebrospinal fluid (CSF) leak that required placement of external drainage systems (ventriculostomy or lumbar drain, or both); 10 (23%) of these 42 patients eventually needed shunt placement to stop the leak because of hydrocephalus. Prior craniotomy, prior radiation therapy, and postoperative CSF infection were also associated with an increased risk of developing hydrocephalus (48% versus 6%, 19% versus 8%, and 14% versus 7%, respectively). Prior radiation and postoperative CSF infection increased the risk of CSF leak in patients with hydrocephalus (30% versus 18% and 30% versus 9%, respectively). CSF leak and hydrocephalus commonly occurred in patients who underwent resection of a glomus tumor. In conclusion, 8% of patients who underwent cranial base surgery for tumors developed de novo hydrocephalus; half of them also had CSF leak in addition to hydrocephalus; and all required shunt placement for CSF diversion.