Molecular monitoring of adenovirus in peripheral blood after allogeneic bone marrow transplantation permits early diagnosis of disseminated disease

Blood ◽  
2003 ◽  
Vol 102 (3) ◽  
pp. 1114-1120 ◽  
Author(s):  
Thomas Lion ◽  
Rosi Baumgartinger ◽  
Franz Watzinger ◽  
Susanne Matthes-Martin ◽  
Magdalena Suda ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Real Time ◽  
Peripheral Blood ◽  
Clinical Symptoms ◽  
Virus Disease ◽  
Antiviral Treatment ◽  
Allogeneic Bone Marrow Transplantation ◽  
Clinical Signs ◽  
Allogeneic Bone ◽  
Disseminated Disease

AbstractAdenovirus (AdV) infection in the course of allogeneic stem cell transplantation (SCT) is associated with high transplant-related morbidity and mortality. Disseminated AdV disease is lethal in most instances. Early detection of AdV infection and identification of patients carrying a high risk of disseminated disease therefore remain a major challenge. In view of the large number of existing AdV types, we have established real-time polymerase chain reaction (PCR) assays permitting sensitive detection and quantification of all 51 currently known human AdV serotypes. In a series of 132 consecutive pediatric patients undergoing SCT, more than 5000 samples derived from peripheral blood (PB), stool, urine, and throat were screened for adenovirus infection by PCR during the posttransplantation period. Thirty-six patients (27%) tested positive by PCR, revealing AdV types of the subgenera A, B, C, D, and F. Except for enteritis in some patients with AdV positivity in stool, detection of the virus at sites other than PB was not associated with clinical signs of virus disease, and transplant-related mortality was not significantly different from AdV-negative patients. By contrast, 82% of patients who had detectable AdV in PB died from infectious complications (P < .001). Monitoring of PB specimens by real-time PCR permitted early diagnosis of invasive AdV infection in all instances. In patients who developed disseminated AdV disease, detection of the virus in PB preceded onset of clinical symptoms by a median of more than 3 weeks. The observation of AdV in peripheral blood may therefore serve as a basis for early initiation of preemptive antiviral treatment.

Delayed Onset of T Cell-Mediated Xenogeneic Disease in Rag2−/− γc−/− mice after Co- Transplantation of in Vitro Expanded Human CD4+CD25highCD45RA+ Regulatory T Cells

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4609-4609
Author(s):  
Tina J Boeld ◽  
Ellen Obermann ◽  
Reinhard Andreesen ◽  
Petra Hoffmann ◽  
Matthias Edinger
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Allogeneic Bone Marrow Transplantation ◽  
Disease Onset ◽  
Clinical Signs ◽  
Allogeneic Bone

Abstract In murine disease models, the adoptive transfer of donor CD4+CD25+ regulatory T cells (Treg) prevents lethal graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation. We recently described methods for the isolation and in vitro expansion of human Treg from adult peripheral blood and found that only CD45RA+ but not CD45RA− CD4+CD25high Treg (RA+ and RA− Treg, respectively) maintain FOXP3 expression as well as suppressive activity after prolonged culture (Hoffmann et al. Blood108:4260; 2006). Here, we compared the immunoregulatory capacity of these two different Treg subpopulations in vivo in a xenogeneic GVHD (xGVHD) model. Transplantation of 20x106 human peripheral blood mononuclear cells (huPBMCs) into immunodeficient BALB/c Rag2−/−γc−/− mice led to engraftment and extensive proliferation of human CD45+ cells (huCD45+), which was accompanied by clinical signs of xGVHD. Histological and flow cytometric evaluation revealed that mainly CD8+ T cells within PBMC caused xGVHD and that main targets were liver, lung and spleen as well as mouse hematopoiesis. When expanded CD45RA+ Treg were co-transplanted at a 1:1 ratio with CD4+ and CD8+ T cells contained in huPBMC, the frequency of huCD45+ cells in peripheral blood (PB) at d14 was reduced to 12 ± 4.9 % (n=15), while animals that received expanded RA− Treg had 30 ± 7.5 % (n=15) and animals without co-transfer of Treg 40 ± 8.3 % (n=14) huCD45+ cells. The expansion of conventional T cells, however, was only delayed but not prevented, as by d21 the percentage of huCD45+ cells in PB increased to 35 ± 9.2 % (n=15) when RA+ Treg were co-transplanted as compared to 40 ± 9.3 % (n=15) with RA− Treg and 50 ± 6.4 % (n=14) without Treg administration. Subsequently, all mice developed clinical signs of xGVHD and 73.3 % of mice co-transplanted with RA+ Treg, 86.7 % co-transplanted with RA− Treg and 78.6 % of mice transplanted with huPBMCs alone died within 100 days. Since Treg mainly inhibited early expansion of huPBMC, we examined the splenic cellularity of xeno-transplanted animals at d10 after cell transfer. While spleens of mice that received only huPBMC contained 20 ± 3x106 huCD45+ cells (n=10), co-transfer of RA− Treg reduced huCD45+ cells to 14 ± 4.8×106 (n=9) whereas animals that received RA+ Treg contained only 5 ± 1.1×106 huCD45+ cells (n=11) at that time. Furthermore, IL-2 and IFN-γ production of conventional T cells re-isolated from the spleen on d10 was reduced 5fold in mice co-transplanted with RA+ Treg as compared to recipients of only huPBMCs or additional RA− Treg. Thus, in vitro expanded human RA+ Treg suppress the proliferation and cytokine production of conventional T cells in early phases of xGVHD, but ultimately do not prevent disease onset and mortality.

scholarly journals Imbalances within the peripheral blood T-helper (CD4+) and T-suppressor (CD8+) cell populations in the reconstitution phase after human bone marrow transplantation

Blood ◽  
1988 ◽  
Vol 71 (5) ◽  
pp. 1196-1200 ◽  
Author(s):  
A Velardi ◽  
A Terenzi ◽  
S Cucciaioni ◽  
R Millo ◽  
CE Grossi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Peripheral Blood ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
T Cell Subsets ◽  
Allogeneic Bone ◽  
T Helper

Abstract Peripheral blood T cell subsets were evaluated in 11 patients during the reconstitution phase after allogeneic bone marrow transplantation and compared with 11 age-matched controls. The proportion of cells coexpressing Leu7 and CD11b (C3bi receptor) markers was determined within the CD4+ (T-helper) and the CD8+ (T-suppressor) subsets by two- color immunofluorescence analysis. CD4+ and CD8+ T cells reached normal or near-normal values within the first year posttransplant. In contrast to normal controls, however, most of the cells in both subsets coexpressed the Leu7 and CD11b markers. T cells with such phenotype display the morphological features of granular lymphocytes (GLs) and a functional inability to produce interleukin 2 (IL 2). These T cell imbalances were not related to graft v host disease (GvHD) or to clinically detectable virus infections and may account for some defects of cellular and humoral immunity that occur after bone marrow transplantation./

scholarly journals Polyclonal primitive hematopoietic progenitors can be detected in mobilized peripheral blood from patients with high-risk myelodysplastic syndromes

Blood ◽  
1995 ◽  
Vol 86 (10) ◽  
pp. 3660-3667 ◽  
Author(s):  
M Delforge ◽  
H Demuynck ◽  
P Vandenberghe ◽  
G Verhoef ◽  
P Zachee ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Myelodysplastic Syndromes ◽  
Peripheral Blood ◽  
Allogeneic Bone Marrow Transplantation ◽  
High Dose ◽  
Allogeneic Bone ◽  
Hematopoietic Progenitors ◽  
Daughter Cells ◽  
Mobilized Peripheral Blood

Myelodysplastic syndromes (MDS) form a heterogeneous group of clonal hematopoietic disorders with unfavourable prognosis. Allogeneic bone marrow transplantation is the only potentially curative treatment, but remains limited to a small subgroup of younger patients with HLA- compatible donors. As autologous stem cell transplantation is currently being explored as an alternative treatment strategy for MDS, more information needs to be acquired regarding the clonal nature of the progenitor cells in these autografts. Therefore, we have analyzed the clonal patterns of highly purified hematopoietic progenitors and their mature daughter cells in mobilized peripheral blood collections produced from five female patients with high-risk MDS in complete hematologic remission. X-chromosome activation patterns of flow-sorted immature (CD34 + 38low, CD34 + 33low) and committed (CD34 + 38high, CD34 + 33high) progenitors were studied with the polymerase chain reaction-based HUMARA assay. In four patients, a polyclonal remission was shown in all stem cell subpopulations and their mature daughter cells whereas one patient was found to remain skewed in all fractions, except T lymphocytes. This study provides strong evidence that polyclonal immature hematopoietic progenitors can be mobilized and harvested in patients high-risk MDS after treatment with high-dose chemotherapy.

Early Diagnosis and Treatment of the Patients with Acquired Hemophagocytic Lymphohistiocytosis

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3552-3552
Author(s):  
Zhao Wang ◽  
Yini Wang ◽  
Cuicui Feng ◽  
Liping Tian
Keyword(s):  
Early Diagnosis ◽  
Diagnostic Criteria ◽  
Peripheral Blood ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Nk Cell ◽  
Clinical Symptoms ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Final Diagnosis ◽  
Nk Cell Activity

Abstract Acquired hemophagocytic lymphohistiocytosis (HLH) is a life threatening condition characterized by uncontroling hyperinflammation on the basis of various infection, tumor and inherited immune deficiency. Awareness of the clinical symptoms and of the diagnostic criteria of HLH is crucial in order not to overlook HLH and to start life-saving therapy in time. In this study, we reviewed 57 suspected HLH patients from March 2006 to June 2008. 25 healthy subjects were enrolled in the study as control. NK cell activity in peripheral blood was tested by a released LDH assay. Meanwhile, solution interleukin-2 receptor (sCD25) was examined with ELISA double antibody sandwich assay. The level of glycosylated ferritin was also detected and the ratio of glycosylated ferritin to ferritin was determined. 41 out of 57 patients were definitely diagnosed according to HLH-2004 diagnostic criteria in this study and 16 patients were excluded. We found that the level of NK cell activity and the ratio of glycosylated ferritin in the all 41 final diagnozed HLH patients were significantly lower than those in the 16 excluded patients and 25 healthy control subjects (p<0.01). Meanwhile, the level of sCD25 in peripheral blood was much higher in all the 41 HLH patients than that in the excluded and healthy people (p<0.05). We compared the coincidence of each diagnostic index in the 41 HLH patients before and after final diagnosis. It was found that 100% patients had abnormal expression on NK cell activity, sCD25 and glycosylated ferritin in the early disease. The three diagnostic indexes were more sensitive and specific than other indexes, such as fever, hepatosplenomegaly, cytopenia, hyper-triglyceridemia, hypo-fibrinogenemia. 41 diagnosed patients received the regimen containing methylprednisolone and immunoglobulin, with or without fludarabine, 26 out of 41 were markedly improved after treatment, 10 out of 41 were exacerbated, and other 5 patients gave up treatment. It is concluded that detection of NK cell activity, sCD25 and glycosylated ferritin may play a very important role in the early diagnosis of HLH. Our data also suggest that fludarabine combined with methylprednisolone and immunoglobulin (FDIg) may provide a new viewpoint for HLH therapy.

scholarly journals Optimization of Early Diagnostics of Prostate Cancer

2020 ◽  
Vol 6 (5) ◽  
pp. 97-104
Author(s):  
N. Stepanov ◽  
Z. Duvayarov ◽  
I, Bystrova ◽  
T. Chepaikina ◽  
V. Kostrova
Keyword(s):  
Prostate Cancer ◽  
Differential Diagnosis ◽  
Early Diagnosis ◽  
Clinical Symptoms ◽  
Clinical Signs ◽  
Diagnostic Errors ◽  
Decay Products ◽  
Examination Methods ◽  
Special Examination ◽  
Diagnostic Capabilities

The prevalence and incidence of prostate cancer is gradually increasing both in our country and in countries near and far abroad. The difficulties in the differential diagnosis of prostate cancer are convincingly evidenced by the fact that the level of diagnostic errors reaches 40%. It should be noted that in assessing the differential diagnostic capabilities of the indicators of the clinical and special examination methods for patients with lower urinary tract symptoms, disagreements were found in 46–77% of the analyzed clinical signs, the changes of which mainly reflect the negative nature of the effect of tumor decay products on the patient’s body. The aim of the study was to improve the early diagnosis of prostate cancer by using the mathematical method of differential diagnosis of prostate pathology, as well as the rationale for the proposed method for early diagnosis of prostate cancer in patients with clinical symptoms. Using our proposed method for early diagnosis of prostate cancer makes the diagnosis not only reliable and accurate, but also independent of the level of qualification of the urologist and his personal experience, allows you to unify, optimize and personify the differential diagnosis of prostatic hypertrophy and prostate cancer.

scholarly journals Arthroscopical treatment of elbow joint disease

2012 ◽  
Vol 64 (1) ◽  
pp. 9-14 ◽  
Author(s):  
C.M.F. Rezende ◽  
E.G. Melo ◽  
C. Malm ◽  
V.A. Gheller
Keyword(s):  
Early Diagnosis ◽  
Osteochondritis Dissecans ◽  
Elbow Joint ◽  
Clinical Symptoms ◽  
Clinical Signs ◽  
Arthroscopic Treatment ◽  
Joint Disease ◽  
Elbow Arthroscopy ◽  
Medial Condyle ◽  
Clinical Recovery

Elbow arthroscopy was performed in 30 dogs of different breeds. The procedure was performed bilaterally in 20 of these dogs, yielding a total of 50 joints. Different lesions were found, varying from cartilage fissures (8) to fragmentation (42) of medial coronoid process (FCP) of the ulna. Osteochondritis dissecans (OCD) of the humerus medial condyle was associated in four of them. All of these cases displayed varying degrees of synovitis. Osteoarthrosis (OA) in varying intensity was observed in 44 joints. The majority of cases were treated two to four months after the manifestation of clinical signs. Good clinical recovery occurred in dogs with minimal joint lesions, where these were diagnosed and treated within four weeks of the onset of clinical symptoms. Early diagnosis and arthroscopic treatment prevent osteoarthrosis and preserve locomotor function.

scholarly journals Clinical manifestations, laboratory markers, and renal ultrasonographic examinations in 1-month to 12-year-old Iranian children with pyelonephritis: a six-year cross-sectional retrospective study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Daryoosh Fahimi ◽  
Leila Khedmat ◽  
Azadeh Afshin ◽  
Zahra Noparast ◽  
Maryam Jafaripor ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Early Diagnosis ◽  
Clinical Symptoms ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Ureteral Stones ◽  
Cross Sectional ◽  
Laboratory Markers ◽  
Febrile Uti ◽  
Iranian Children

Abstract Background Upper urinary tract infection (UTI) or pyelonephritis may increase the pathogenesis rate and risk of severe complications in children due to kidney atrophy. Objective A set of clinical symptoms, laboratory markers, and ultrasound findings were assessed to achieve the early diagnosis and prognosis of pyelonephritis in hospitalized pediatrics. Methods A cross-sectional study with 104 Iranian children (95 girls and 9 boys) aged 1 month to 12 years with acute pyelonephritis during 2012–2018 was conducted. The ultrasound examination of kidneys and urinary tract during hospitalization, the incidence of clinical symptoms, and laboratory markers in blood and urine were monitored to identify the best predictive factors of early diagnosis of this bacterial infection. Results Three-fourth of the patients had one of the four clinical symptoms of abdominal pain, constipation, dysuria, and vomiting, while others were asymptomatic. A much frequency of pyuria (88.46%), Escherichia coli in urine (92.31%), leukocytosis (81.73%), and high ESR (> 10 mm/h, 92.30%) and CRP (> 10 mg/L, 82.82%) was observed. The kidney and urinary tract ultrasonography only in 32.7% of children revealed findings in favor of pyelonephritis (cystitis, ureteral stones, and hydronephrosis). Conclusion There was a high frequency of clinical signs and laboratory markers associated with pyelonephritis. Ultrasound alone was not an efficient tool to track febrile UTI as most patients presented normal sonography.

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