Evidence from a leukaemia model for maintenance of vascular endothelium by bone-marrow-derived endothelial cells.

BACKGROUND: Vascular endothelial cells lost from the blood-vessel endothelium through necrosis or apoptosis must be replaced. We investigated in a leukaemia model whether bone-marrow-derived endothelial cells contribute to this maintenance angiogenesis. METHODS: We studied six patients with chronic myelogenous leukaemia (CML) carrying the BCR/ABL fusion gene in their bone-marrow-derived cells. We screened endothelial cells generated in vitro from bone-marrow-derived progenitor cells and vascular endothelium in myocardial tissue for the BCR/ABL fusion gene by in-situ hybridisation. For detection of donor-type endothelial cells after transplantation of haemopoietic stem cells, recipient tissue was stained with monoclonal antibodies against donor-type HLA antigens. FINDINGS: We identified the BCR/ABL fusion gene in variable proportions (0-56%) of endothelial cells generated in vitro. Endothelial cells expressing the fusion gene were found in the vascular endothelium of a patient. In a recipient of an allogeneic stem-cell transplant, normal donor-type endothelial cells were detected in the vascular endothelium. INTERPRETATION: These findings suggest that CML is not solely a haematological disease but originates from a bone-marrow-derived haemangioblastic precursor cell that can give rise to both blood cells and endothelial cells. Moreover, normal bone-marrow-derived endothelial cells can contribute to the maintenance of the blood vascular endothelium. The integration of bone-marrow-derived endothelial cells into the vascular endothelium provides a rationale for developing vascular targeting strategies in vasculopathies, inflammatory diseases, and cancer.

Blood-derived macrophage layers in the presence of hydrocortisone support myeloid progenitors in long-term cultures of CD34+ cord blood and bone marrow cells.

Monocytes/macrophages secrete various cytokines that induce proliferation of colony-forming unit granulocyte-macrophage (CFU-GM) in short-term assays. To determine whether macrophages also support proliferation of more primitive progenitors, i.e., cells that give rise to colony forming cells in a 5-week long-term culture (LTC), we established plastic-adherent macrophage layers from human peripheral blood (PB) and filgrastim (G-CSF)-mobilized progenitor cell collections in the presence of hydrocortisone, and compared these layers with bone marrow (BM) stroma regarding their suitability to support proliferation and differentiation of CD34+ BM and cord blood (CB) cells in 5-week LTCs. CD34+ cells were seeded onto irradiated macrophage and BM stromal layers, as well as without any preformed layer. After 5 weeks, colony formation (CFU-GM, BFU-E/CFU-E) and cell expansion were determined. CD34+ cells from BM and CB yielded more CFU-GM and total nucleated cells at 5 weeks in the presence of both types of adherent layer compared with cultures without a layer (p<0.05). For CD34+ BM cells, macrophage layers were superior to BM stroma in enhancing CFU-GM and CFU-E/BFU-E output (p < 0.05). In contrast, BM stroma was favorable compared with macrophages concerning nucleated cell expansion from CD34+ CB cells (p = 0.027). The macrophage nature of PB-derived adherent cells was confirmed immunocytochemically by positive staining for CD68, Ki-Mlp, CD31, CD54, inconstant staining for CD14, and negative staining for CD1a, CD3, CD15, CD34, and CD62E. Cytochemical reactions were positive for alpha-naphthyl acetate esterase and negative for peroxidase and periodic acid-Schiff, consistent with the immunophenotype. In conclusion, the results show that blood-derived macrophages support CFU-GM generation from CD34+ CB and BM progenitors for 5 weeks in vitro. Differential effects on proliferation and maturation of BM versus CB progenitors are discussed.

Aspergillus osteoarthritis in acute lymphoblastic leukemia.

We report an unusual case of arthritis of the right wrist due to Aspergillus fumigatus without evidence for a generalized infection, following chemotherapy for acute lymphoblastic leukemia. The diagnosis was made by surgical biopsy. Amphotericin-B (Am-B) was not tolerated by the patient. Liposomal preparations of Am-B penetrate poorly into bone and cartilage. Therefore, oral itraconazole was given; the arthritis improved and chemotherapy was continued without infectious complications. Two weeks after complete hematopoietic recovery, an intracranial hemorrhage from a mycotic aneurysm of a brain vessel occurred, although the patient was still receiving itraconazole. We emphasize the importance of prompt and thorough efforts to identify the causative agent in immunocompromised patients with a joint infection. Itraconazole is effective in Aspergillus osteoarthritis but, due to its poor penetration into the brain, the combination with a liposomal formulation of Am-B is recommended.

Mean weighted nuclear volumes in colonic adenocarcinomas. Evaluation of prognostic significance.

OBJECTIVE: To investigate the correlation of stereologically estimated mean weighted nuclear volumes of tumor cell nuclei (MWNV) with other prognostic factors and survival in colonic adenocarcinomas. STUDY DESIGN: The study group consisted of 42 patients with colonic adenocarcinomas who were treated by a standardized protocol and had a mean follow-up of 89 months. The point sample intercepts method was used to estimate MWNV. In addition, immunohistochemical expression of p53 and Ki-67 was evaluated semiquantitatively. RESULTS: The calculated nuclear volumes correlated significantly with histologic grading and with the extent of tumor progression (organ confined/nonorgan confined). There was no correlation with p53 expression or proliferative activity determined by MIB-1 positivity. No correlation could be demonstrated with sex, age or clinical outcome of the patients. CONCLUSION: Assessment of MWNV in colonic adenocarcinomas does not provide additional information concerning the clinical course.

Urticaria pigmentosa: a clinical, hematopathologic, and serologic study of 30 adults.

Urticaria pigmentosa (UP) is the most common form of cutaneous mastocytosis and may be associated with systemic involvement, most often of the bone marrow. The incidence of systemic involvement is not yet well established, however. To address this question, we subjected a group of 30 adults with histologically proved UP to a retrospective study that included history, physical examination, laboratory tests including cytokine measurements, radiologic examinations, and bone marrow biopsies. The most frequently associated clinical symptoms were recurrent flush episodes in 16 of 30 patients, alcohol intolerance in 13, pruritus in 10, and gastrointestinal problems in 11 (recurrent diarrhea, 8 patients; gastritis, 2 patients; and history of peptic ulcer, 1 patient). Of the 30 patients, 18 (60%) had mast cell infiltrates of the bone marrow (nodular type, 10 patients; diffuse interstitial type, 8 patients). Bone marrow involvement was not correlated with massive cutaneous mast cell infiltration, clinically or histologically, or with the incidence of clinical symptoms and associated hematologic disorders. None of the patients had experienced progression of clinical symptoms, skin or organ involvement, or development of hematologic malignant neoplasms since UP was first diagnosed (10 years on average). Urticaria pigmentosa was found associated with mast cell infiltration of the bone marrow in 18 patients (60%). However, bone marrow involvement does not seem to predict adverse clinical course.

What do physicians think of telemedicine? A survey in different European regions.

To discover the perception of telemedicine in a sample of physicians not yet participating in telemedicine networks, a questionnaire was sent to doctors in different European countries. The questions covered various general aspects of telemedicine. The percentage of questionnaires returned ranged from 12% (Central Europe) to 27% (Spain). Apart from the rather disappointing response rates the results document a strong interest in telemedicine on the part of the physicians surveyed. Knowledge of the existence of telemedicine was high. Most of the respondents would have liked to have had their clinic's telemedicine system in their own laboratory. More than 50% of the physicians thought that their work would be improved by using telemedicine. Respondents from Central Europe were significantly less enthusiastic about telemedicine than those from other regions. However, the answers to the majority of the questions were similar in the different groups.

Gastric malt lymphoma with crystalline immunoglobulin inclusions and secondary immunoblastic lymphoma in a cervical lymph node.

A case of gastric B cell lymphoma of the mucosa-associated lymphoid tissue (MALT) with crystalline immunoglobulin inclusions in monotypic plasma cells is reported, which initially presented as a secondary immunoblastic lymphoma in a cervical lymph node. The low-grade MALT lymphoma was diagnosed 14 months after detection of the nodal high-grade lymphoma, but rare crystal-containing plasma cells of identical immunoglobulin isotype found in the immunoblastic lymphoma retrospectively confirmed a common clonal origin. The diagnostic significance of crystalline immunoglobulin inclusions and the unusual initial presentation of MALT lymphoma as a secondary high-grade lymphoma at a distant nodal site are discussed.

Detection of intralesional calcium by intracoronary ultrasound depends on the histologic pattern.

This study was designed to examine the accuracy of intravascular ultrasound in detecting different histologic types of calcium pattern in human coronary artery atherosclerotic lesions. Previous studies have shown that calcium deposits in atherosclerotic lesions may occur in various forms and that intravascular ultrasound is a sensitive technique to detect calcium in atherosclerotic lesions. However, there has been no distinction between varying image representations of calcium and different histologic patterns of intralesional calcific deposits. Calcific lesions have an important clinical impact on the outcome of intracoronary transcatheter therapy, and the varying types of calcium may also play a role in the guidance of intracoronary interventions. Fifty fresh coronary vessel segments were studied by intracoronary ultrasound imaging and the images compared with the corresponding histologic sections. With intracoronary ultrasound imaging, calcium was defined as bright echo with corresponding sharp edged shadowing in the distal field. Three different histologic types of calcification were defined, and the sensitivity and specificity of the detection by intravascular ultrasound were determined for each type. Dense calcified plaques (type 1) were found 18 cases, microcalcification (small flecks of calcium) with single calcium fleck size < or = 0.05 mm (type 2) in 12 cases, and combination of calcified plaque surrounded by small calcium flecks (type 3) in 3 cases. In 17 (34%) coronary vessel segments, histologic analyses detected no calcium. Intracoronary ultrasound correctly detected 16 (89%) of 18 cases of type 1 calcification, 2 (17%) of 12 type 2, and all 3 (100%) type 3. Sensitivity for detection of type 1 and 3 calcification was 90%, with specificity of 100%.(ABSTRACT TRUNCATED AT 250 WORDS)